Substituted indole compounds

ABSTRACT

Substituted indole compounds corresponding to the formula I: 
                         
In which R 8 , R 9a , R 9b , R 10 , R 11 , R 200 , R 210 , A, D, T, q, s and t have defined meanings, processes for the preparation thereof, pharmaceutical compositions containing such compounds and the use of substituted indole compounds for the treatment or inhibition of pain and other conditions which are at least partly mediated by Bradykinin 1 receptors (B1R).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from co-pending provisional applicationNo. 61/149,785, filed Feb. 4, 2009. Priority is also claimed based onEuropean patent application no. EP 09001488.7, likewise filed Feb. 4,2009.

BACKGROUND OF THE INVENTION

The present invention relates to substituted indole compounds, processesfor the preparation thereof, medicinal products containing thesecompounds and the use of substituted indole compounds for thepreparation of medicinal products.

In contrast to the constitutive expression of the bradykinin 2 receptor(B2R), the bradykinin 1 receptor (B1R) is not expressed or is onlyweakly expressed in most tissues. Nevertheless, expression of the B1Rcan be induced on various cells. By way of example, in the course ofinflammation reactions a rapid and pronounced induction of the B1R takesplace on neuronal cells, but also on various peripheral cells, such asfibroblasts, endothelial cells, granulocytes, macrophages andlymphocytes. Thus, in the course of inflammation reactions a switch froma B2R to a B1R dominance occurs on the cells involved. The cytokinesinterleukin-1 (IL-1) and tumour necrosis factor alpha (TNFα) aresubstantially involved in this B1R up-regulation (Passos et al. J.Immunol. 2004, 172, 1839-1847). After activation with specific ligands,B1R-expressing cells can subsequently themselves secreteinflammation-promoting cytokines, such as IL-6 and IL-8 (Hayashi et al.,Eur. Respir. J. 2000, 16, 452-458). This leads to inwards migration offurther inflammation cells, for example neutrophilic granulocytes(Pesquero et al., PNAS 2000, 97, 8140-8145). The bradykinin B1R systemcan contribute to the chronification of diseases via these mechanisms.This is demonstrated by a large number of animal studies (overviews inLeeb-Lundberg et al., Pharmacol Rev. 2005, 57, 27-77 and Pesquero etal., Biol. Chem. 2006, 387, 119-126). In humans too, an increasedexpression of the B1R is seen, for example on enterocytes andmacrophages in the affected tissue of patients with inflammatory boweldiseases (Stadnicki et al., Am. J. Physiol. Gastrointest. Liver Physiol.2005, 289, G361-366) and on T lymphocytes of patients with multiplesclerosis (Pratet al., Neurology. 1999; 53, 2087-2092), or an activationof the bradykinin B2R-B1R system is seen in the course of infectionswith Staphyloccocus aureus (Bengtson et al., Blood 2006, 108,2055-2063). Infections with Staphyloccocus aureus are responsible fordisease profiles such as superficial infections of the skin through toseptic shock.

Based on the pathophysiological relationships described, there is greattherapeutic potential for the use of B1R antagonists against acute andin particular chronic inflammatory diseases. They include diseases ofthe respiratory tract (bronchial asthma, allergies, COPD/chronicobstructive pulmonary disease, cystic fibrosis, etc.), inflammatorybowel diseases (ulcerative colitis, CD/Crohn's disease, etc.),neurological diseases (multiple sclerosis, neurodegeneration, etc.),inflammations of the skin (atopic dermatitis, psoriasis, bacterialinfections, etc.) and mucous membranes (Behcet's disease, chronic pelvicpain, prostatitis, etc.), rheumatic diseases (rheumatoid arthritis,osteoarthritis, etc.), septic shock and reperfusion syndrome (followingheart attack or stroke).

The bradykinin (receptor) system is moreover also involved in theregulation of angiogenesis (potential as an angiogenesis inhibitor incases of cancer and macula degeneration in the eye), and B1R-knockoutmice are protected from the induction of obesity by a particularlyhigh-fat diet (Pesquero et al., Biol. Chem. 2006, 387, 119-126). B1Rantagonists are therefore also suitable for the treatment of obesity.

B1R antagonists are particularly suitable for the treatment of pain, inparticular inflammatory pain and neuropathic pain (Calixto et al., Br.J. Pharmacol 2004, 1-16), and here in particular diabetic neuropathy(Gabra et al., Biol. Chem. 2006, 387, 127-143). They are also suitablefor the treatment of migraine.

In the development of B1R modulators there is the problem, however, thatthe human and the rat B1R receptor differ so widely that many compoundswhich are good B1R modulators on the human receptor have only a poor orno affinity for the rat receptor. This makes animal pharmacology studiesconsiderably more difficult, since many studies are usually conducted onthe rat. However, if there is no activity on the rat receptor, neitheraction nor side-effect can be investigated on the rat. This has alreadymeant that transgenic animals with human B1 receptors have been producedfor animal pharmacology studies (Hess et al., Biol. Chem. 2006;387(2):195-201). Working with transgenic animals is, however, moreexpensive than working with the unmodified animals.

International patent applications WO 2008/040492 and WO 2008/046573describe compounds which in in-vitro assays exhibit an antagonisticaction both on the human B1 receptor and on the B1 receptor of the rat.

International patent applications WO 2007/140383 and WO 2007/101007describe compounds which in in-vitro assays exhibit an antagonisticaction on the macaque B1 receptor. Experimental data on the activity onthe human B1 receptor or the B1 receptor of the rat is not disclosed.

Despite the efforts of the prior art, there remains a need for novel B1Rmodulators, whereby B1R modulators which bind both to the rat receptorand to the human receptor offer particular advantages.

SUMMARY OF THE INVENTION

An object of the present invention was therefore to provide novelcompounds which are suitable in particular as pharmacological activeingredients in medicinal products, preferably in medicinal products forthe treatment of disorders or diseases which are at least partlymediated by B1R receptors.

This object is achieved by the substituted indole compounds according tothe invention.

The invention therefore provides substituted indole compounds having theformula (I)

wherein

-   T denotes CH or N;-   q=1, 2 or 3;-   s=0 or 1;-   t=0, 1, 2 or 3;-   D in position a or b is bound to the indole skeleton and denotes one    of the following groups D1 or D2

wherein

-   x and y, each independently, denote 0 or 1;-   r denotes 1, 2 or 3;-   Q₁ and Q₂ each independently denote C, CH or N;-   R¹ and R² together with the -Q₁-Q₂-group linking them form a cyclic    compound, which can be substituted at one or more of its carbon ring    members with one or more substituents independently selected from    the group consisting of F, Cl, Br, I, CF₃, C₁₋₆ alkyl, O—C₁₋₆ alkyl,    OH, OCF₃, SH, SCF₃, aryl and heteroaryl and/or can be anellated with    at least one aryl or heteroaryl, wherein the cyclic compound is    saturated, mono- or polyunsaturated, for example diunsaturated, or    aromatic, is 4-, 5-, 6- or 7-membered, can optionally contain one or    more, for example 2 or 3, heteroatoms or heteroatom groups each    independently selected from the group consisting of N, NR⁵⁰, O, S,    S═O and S(═O)₂; wherein R⁵⁰ denotes H, C₁₋₆ alkyl, —C(═O)—R⁵¹, C₃₋₈    cycloalkyl, aryl, heteroaryl or a C₃₋₈ cycloalkyl, aryl or    heteroaryl bound via a C₁₋₃ alkylene group, and R⁵¹ denotes C₁₋₆    alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl or a C₃₋₈ cycloalkyl, aryl    or heteroaryl bound via a C₁₋₃ alkylene group;-   R³ denotes aryl, heteroaryl or an aryl or heteroaryl bound via a    C₁₋₃ alkylene group, wherein aryl and heteroaryl can each be    anellated with a 4-, 5-, 6- or 7-membered cyclic compound, wherein    the cyclic compound is in each case saturated or mono- or    polyunsaturated, for example diunsaturated, but is not aromatic and    can be substituted at one or more of its carbon ring members with    one or more substituents independently selected from the group    consisting of F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₆ alkyl and O—C₁₋₆    alkyl and can optionally contain one or more, for example 2 or 3,    heteroatoms or heteroatom groups each independently selected from    the group consisting of N, NR^(50a), O, S, S═O and S(═O)₂, wherein    R^(50a) denotes H, C₁₋₆ alkyl, —C(═O)—R^(51a), C₃₋₈ cycloalkyl,    aryl, heteroaryl or a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via    a C₁₋₃ alkylene group and R^(51a) denotes C₁₋₆ alkyl, C₃₋₈    cycloalkyl, aryl, heteroaryl or a C₃₋₈ cycloalkyl, aryl or    heteroaryl bound via a C₁₋₃ alkylene group;-   R⁴ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or a    C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group;-   R²⁰⁰ denotes 0 to 2 substituents, which are each independently    selected from the group consisting of F, Cl, Br, I, CF₃, OCF₃, OH,    O—C₁₋₆ alkyl, C₁₋₆ alkyl, aryl and heteroaryl and/or two adjacent    substituents R²⁰⁰ form an anellated aryl or heteroaryl;-   R²¹⁰ denotes 0 to 3 substituents which are each independently    selected from the group consisting of F, Cl, Br, I, CF₃, OCF₃, OH,    O—C₁₋₆ alkyl, C₁₋₆ alkyl, aryl and heteroaryl;-   R⁸ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or a    C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group;-   R^(9a) and R^(9b) each independently denote H, F, Cl, OH, C₁₋₆    alkyl, O—C₁₋₆ alkyl, C₁₋₃ cycloalkyl, aryl or heteroaryl or a C₃₋₈    cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group;-   A denotes N or CH;-   with the proviso that if s denotes 1 and t denotes 0 then A denotes    CH; and-   with the proviso that if s and t each denote 0 then A denotes N;-   R¹⁰ and R¹¹ together with A represent a spirocyclic or cyclic group    according to one of the formulas (II) or (III),

wherein

-   c, d, e, f, u and v each independently denote 0, 1 or 2;-   R¹², R¹³ and R²⁷ each independently denote 0 to 4 substituents which    are each independently selected from the group consisting of F, Cl,    OH, ═O, C₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl    and C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene    group; and/or    -   two of the 0 to 4 substituents R²⁷ together represent a C₁₋₃        alkylene bridge such that the cyclic compound represented in the        formula (III) assumes a bicyclically bridged form; and/or    -   two adjacent substituents out of the 0 to 4 substituents R¹³        form an anellated aryl or heteroaryl group; and/or    -   two adjacent substituents out of the 0 to 4 substituents R²⁷        form an anellated aryl or heteroaryl group;-   X denotes CR^(14a)R^(14b), NR¹⁵ or O;-   Y denotes CR^(16a)R^(16b), NR¹⁷ or O;-   with the proviso that X does not denote NR¹⁵ if Y denotes NR¹⁷; and-   with the proviso that X and Y do not simultaneously denote 0;    wherein-   R^(14a), R^(14b), R^(16a) and R^(16b) each independently denote H,    F, Cl, OH, C₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or    heteroaryl or denote a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via    a C₁₋₆ alkylene group, and/or-   R^(14a) and R^(14b) can together denote ═O, and/or-   R^(16a) and R^(16b) can together denote ═O;-   R¹⁵ and R¹⁷ each independently denote H, C₁₋₆ alkyl, C₃₋₈    cycloalkyl, aryl or heteroaryl or denote a C₃₋₈ cycloalkyl, aryl or    heteroaryl bound via a C₁₋₆ alkylene group;-   Z in formula (II) denotes CR^(18a)R^(18b), NR¹⁹ or O, or-   Z in formula (II), if X denotes O and f denotes 0, denotes    —(C(R¹²⁴)—C(R¹²⁵))—, wherein R¹²⁴ and R¹²⁵ together with the carbon    atoms linking them form a fused aryl or heteroaryl group; or-   Z in formula (II), if X denotes O and f denotes 0, denotes    ═(N(CR¹²⁶))—, wherein the N atom is singly bonded to the O atom, and-   R¹²⁶ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆    alkylene group;-   Z in formula (III) denotes CR^(18a)R^(18b), NR¹⁹, O, S, S(═O) or    S(═O)₂;    wherein-   R^(18a) denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl    or denotes a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆    alkylene group, or-   R^(18a) denotes a group according to the formula (IV),

wherein

-   i and j each independently denote 0 or 1;-   E denotes N or CH, with the proviso that if i denotes 1 and j    denotes 0 then E denotes CH;-   R³⁴ and R³⁵ each independently denote H, C₁₋₆ alkyl, C₃₋₈    cycloalkyl, aryl or heteroaryl or an aryl, heteroaryl or C₃₋₈    cycloalkyl bound via a C₁₋₃ alkylene group; or-   R³⁴ and R³⁵ with inclusion of E form a 5- or 6-membered aryl or    heteroaryl; or-   R³⁴ and R³⁵ with inclusion of E form a saturated heterocyclic    compound according to the formula (V),

wherein

-   h and g each independently denote 0, 1 or 2;-   G denotes CR^(37a)R^(37b), NR³⁸, O, S, S═O or S(═O)₂, with the    proviso that if E denotes CH then G does not denote CR^(37a)R^(37b);-   R³⁶ denotes 0 to 4 substituents each independently selected from the    group consisting of F, Cl, Br, I, OH, SH, ═O, O—C₁₋₆ alkyl, C₁₋₆    alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl and C₃₋₈ cycloalkyl, aryl    or heteroaryl bound via a C₁₋₆ alkylene group; and/or two adjacent    substituents R³⁶ together represent an anellated aryl or heteroaryl;-   R^(37a) and R^(37b) each independently denote H, F, Cl, Br, I, OH,    SH, ═O, O—C₁₋₆ alkyl, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or    heteroaryl or denote a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via    a C₁₋₆ alkylene group;-   R³⁸ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes an aryl, heteroaryl or C₃₋₈ cycloalkyl bound via a C₁₋₃    alkylene group;-   R^(18b) denotes H, OH, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, O—C₁₋₆ alkyl,    O—(C₃₋₈ cycloalkyl), (C₁₋₆ alkylene)-O—C₁₋₆ alkyl, (C₁₋₆    alkylene)-O—(C₃₋₈ cycloalkyl), aryl, heteroaryl, O-aryl or    O-heteroaryl or denotes an aryl, O-aryl, heteroaryl or O-heteroaryl    bound via a C₁₋₆ alkylene group; or-   R^(18b) denotes a group according to the formula (VI),

wherein

-   k denotes 0 or 1;-   R³⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₃    alkylene group;-   R⁴⁰ denotes C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆    alkylene group; or-   R³⁹ and R⁴⁰ together with the N−C(═O) group linking them form a ring    according to the formula (VII),

wherein

-   I denotes 0, 1 or 2; and-   R⁴¹ and R⁴² together with the carbon atoms linking them form an    anellated aryl or heteroaryl;-   R¹⁹ denotes H; or (P)_(z)—R²²,    wherein-   z denotes 0 or 1;-   P denotes (C═O), S(═O)₂ or C(═O)—N(R²⁴), wherein the N atom in the    C(═O)—N(R²⁴) group is linked to R²², wherein-   R²⁴ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or an aryl, heteroaryl or    C₃₋₈ cycloalkyl bound via a C₁₋₆ alkylene group;-   R²² denotes C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes an aryl or heteroaryl bound via a C₁₋₆ alkylene group; or-   R²² denotes a group according to the formula (VIII), wherein

-   n denotes 0, 1 or 2;-   m denotes 0, 1 or 2;-   w denotes 0 or 1, and-   M denotes CH or N;-   with the proviso that if P denotes C(═O)—NR²⁴, and w denotes 0, then    M denotes CH; and-   with the proviso that if z and w simultaneously denote 0 then M    denotes CH;-   L denotes CR^(44a)R^(44b), NR⁴⁵, O, S, S═O or S(═O)₂;-   R⁴³ denotes 0 to 4 substituents each independently selected from the    group consisting of F, Cl, OH, ═O, C₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈    cycloalkyl, aryl, heteroaryl and C₃₋₈ cycloalkyl, aryl or heteroaryl    bound via a C₁₋₆ alkylene group; and/or two adjacent substituents    out of the 0 to 4 substituents R⁴³ together represent an anellated    aryl or heteroaryl ring structure;-   R^(44a) and R^(44b) each independently denote H, F, Cl, Br, I, OH,    C₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denote a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆    alkylene group; or-   R^(44a) and R^(44b) can together denote ═O;-   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or    denotes an aryl, heteroaryl or C₃₋₈ cycloalkyl bound via a C₁₋₃    alkylene group;    wherein the aforementioned C₁₋₆ alkyl, C₁₋₃ alkylene, C₁₋₆ alkylene,    C₃₋₈ cycloalkyl, aryl and heteroaryl groups may each be    unsubstituted or mono- or polysubstituted with identical or    different substituents and the aforementioned C₁₋₆ alkyl, C₁₋₃    alkylene and C₁₋₆ alkylene groups may each be branched or    unbranched;    optionally in the form of an isolated enantiomer or an isolated    diastereomer, the racemate, the enantiomers, the diastereomers,    mixtures of enantiomers and/or diastereomers, and each in the form    of their bases and/or physiologically compatible salts.

In the formula (IV) used above, the bonds shown between E and R³⁴ andR³⁵ should not be understood exclusively as single bonds; they can alsobe part of an aromatic system.

Within the meaning of the present invention the term “halogen”preferably denotes F, Cl, Br and I, in particular F and Cl.

Within the meaning of this invention, the expression “C₁₋₆ alkyl”includes acyclic saturated hydrocarbon groups having 1, 2, 3, 4, 5 or 6carbon atoms, which may be branched or straight-chain (unbranched) andunsubstituted or mono- or polysubstituted, for example di-, tri-, tetra-or pentasubstituted, with identical or different substituents. The alkylgroups are preferably selected from the group consisting of methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,n-pentyl, isopentyl, neopentyl and hexyl. Particularly preferred alkylgroups are selected from the group consisting of methyl, ethyl,n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl.

Within the meaning of this invention, the expression “C₃₋₈ cycloalkyl”denotes cyclic saturated hydrocarbons having 3, 4, 5, 6, 7 or 8 carbonatoms, which may be unsubstituted or mono- or polysubstituted, forexample di-, tri-, tetra- or pentasubstituted, at one or more ringmembers with identical or different substituents. C₃₋₈ cycloalkyl ispreferably selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

Within the meaning of this invention, the expression “aryl” denotesaromatic hydrocarbons, in particular phenyls and naphthyls. The arylgroups may also be fused to other saturated, (partially) unsaturated oraromatic ring systems. Each aryl group may be present in unsubstitutedor mono- or polysubstituted form, for example di-, tri-, tetra- orpentasubstituted, wherein the aryl substituents can be identical ordifferent and can be at any desired and possible position of the arylgroup. Aryl is advantageously selected from the group consisting ofphenyl, 1-naphthyl and 2-naphthyl, each of which may be unsubstituted ormono- or polysubstituted, for example with 2, 3, 4 or 5 substituents.

Within the meaning of the present invention, the expression “heteroaryl”denotes a 5-, 6- or 7-membered cyclic aromatic group containing at least1, optionally also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms maybe identical or different and the heteroaryl can be unsubstituted ormono- or polysubstituted, for example di-, tri-, tetra- orpentasubstituted, with identical or different substituents. Thesubstituents can be bound to any desired and possible position of theheteroaryl group. The heterocyclic compound can also be part of abicyclic or polycyclic ring system, in particular a mono-, bi- ortricyclic system, which can then in total be more than 7-membered, forexample up to 14-membered. Preferred heteroatoms are selected from thegroup consisting of N, O and S. The heteroaryl group is preferablyselected from the group consisting of pyrrolyl, indolyl, furyl(furanyl), benzofuranyl, thienyl (thiophenyl), benzothienyl,benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl,benzodioxanyl, benzooxazolyl, benzooxadiazolyl, imidazothiazolyl,dibenzofuranyl, dibenzothienyl, phthalazinyl, pyrazolyl, imidazolyl,thiazolyl, oxazolyl, oxadiazolyl, triazole, tetrazole, isoxazolyl,pyridinyl (pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl,indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl,quinazolinyl, quinoxalinyl, carbazolyl, phenazinyl, phenothiazinyl andoxadiazolyl; particularly preferably from the group consisting ofthienyl (thiophenyl), pyridinyl (pyridyl), pyrimidinyl, thiazolyl,triazolyl, imidazolyl, oxazolyl, oxadiazolyl, quinazolinyl, quinolinyland isoquinolinyl, wherein the bond to the general structure (I) can bemade via any desired and possible ring member of the heteroaryl group.The heteroaryl group is especially preferably selected from the groupconsisting of thienyl, imidazolyl, thiazolyl, triazolyl, pyridinyl andpyrimidinyl.

Within the meaning of the present invention, the expression “C₁₋₃alkylene group” or “C₁₋₆ alkylene group” includes acyclic saturatedhydrocarbon groups having respectively 1, 2 or 3 or 1, 2, 3, 4, 5 or 6carbon atoms, which can be branched or straight-chain (unbranched) andunsubstituted or mono- or polysubstituted, for example di-, tri-, tetra-or pentasubstituted, with identical or different substituents, and whichlink a respective group to the higher-order general structure. Thealkylene groups are preferably selected from the group consisting of—CH₂—, —CH₂—CH₂—, —CH(CH₃)—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—, —CH(CH₂CH₃)—,—CH₂—(CH₂)₂—CH₂—, —CH(CH₃)—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—,—CH(CH₃)—CH(CH₃)—, —CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH₂—, —CH(CH₂CH₂CH₃)—,—C(CH₃)(CH₂CH₃)—, —CH₂—(CH₂)₃—CH₂—, —CH(CH₃)—CH₂—CH₂—CH₂—,—CH₂—CH(CH₃)—CH₂—CH₂—, —CH(CH₃)—CH₂—CH(CH₃)—, —CH(CH₃)—CH(CH₃)—CH₂—,—C(CH₃)₂—CH₂—CH₂—, —CH₂—C(CH₃)₂—CH₂—, —CH(CH₂CH₃)—CH₂—CH₂—,—CH₂—CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH(CH₃)—, —CH(CH₂CH₃)—CH(CH₃)—,—C(CH₃)(CH₂CH₃)—CH₂—, —CH(CH₂CH₂CH₃)—CH₂—, —C(CH₂CH₂CH₃)—CH₂—,—CH(CH₂CH₂CH₂CH₃)—, —C(CH₃)(CH₂CH₂CH₃)—, —C(CH₂CH₃)₂— and—CH₂—(CH₂)₄—CH₂—. The alkylene groups are particularly preferablyselected from the group consisting of —CH₂—, —CH₂—CH₂— and—CH₂—CH₂—CH₂—.

Within the meaning of the present invention the expression“—(O)_(0/1)—C₁₋₆ alkylene group” also includes in addition to the C₁₋₆alkylene groups described above such groups in which these groups arelinked by an oxygen atom to the higher-order structure.

Within the meaning of the present invention, the expression “aryl orheteroaryl bound via a C₁₋₃ alkylene group or a C₁₋₆ alkylene group”means that the C₁₋₃ alkylene groups, C₁₋₆ alkylene groups and aryl orheteroaryl have the meanings defined above and the aryl or heteroarylgroup is bound to the higher-order general structure by a C₁₋₃ alkylenegroup or C₁₋₆ alkylene group. Benzyl, phenethyl and phenylpropyl arecited by way of example.

Within the meaning of the present invention, the expression “C₃₋₈cycloalkyl bound via a C₁₋₃ alkylene group or C₁₋₆ alkylene group” meansthat the C₁₋₃ alkylene group, C₁₋₆ alkylene group and C₃₋₈ cycloalkylhave the meanings defined above and C₃₋₈ cycloalkyl is bound via a C₁₋₃alkylene group or C₁₋₆ alkylene group to the higher-order generalstructure.

In connection with “alkyl”, “alkylene” and “cycloalkyl”, the term“substituted” within the meaning of this invention is understood to meanthe replacement of a hydrogen with F, Cl, Br, I, CF₃, OCF₃, CN, NH₂,NH—C₁₋₆ alkyl, NH—C₁₋₆ alkylene-OH, C₁₋₆ alkyl, N(C₁₋₆ alkyl)₂, N(C₁₋₆alkylene-OH)₂, NO₂, SH, S—C₁₋₆ alkyl, C₁₋₆ alkyl, S-benzyl, O—C₁₋₆alkyl, OH, O—C₁₋₆ alkylene-OH, ═O, O-benzyl, C(═O)C₁₋₆ alkyl, CO₂H,CO₂—C₁₋₆ alkyl, phenyl, phenoxy, benzyl, naphthyl, furyl, thienyl andpyridinyl, wherein polysubstituted groups are understood to mean groupswhich are substituted multiple times, for example twice or three times,at different or the same atoms, for example substituted three times atthe same C atom, as in the case of CF₃ or —CH₂CF₃, or at differentsites, as in the case of CH(Cl)—CH═CH—OHCl₂. The polysubstitution cantake place with identical or different substituents, as for example inthe case of CH(OH)—CH═CH—CHCl₂. It should be understood in particular tobe the replacement of one or more hydrogens with F, Cl, NH₂, OH, phenyl,O—CF₃ or O—C₁₋₆ alkyl, in particular methoxy.

In connection with “aryl” and “heteroaryl”, the term “substituted”within the meaning of this invention is understood to mean thereplacement of one or more hydrogen atoms of the respective ring system,including mono- or polysubstitution, for example the di-, tri-, tetra-or pentasubstitution, with F, Cl, Br, I, CN, NH₂, NH—C₁₋₆ alkyl, NH—C₁₋₆alkylene-OH, N(C₁₋₆ alkyl)₂, N(C₁₋₆ alkylene-OH)₂, NH aryl¹, N(aryl¹)₂,N(C₁₋₆ alkyl)aryl¹, pyrrolinyl, piperazinyl, morpholinyl, azetidinyl,piperidinyl, thiazolinyl, azepanyl, diazepanyl, (C₁₋₃alkylene)-azetidinyl, (C₁₋₃ alkylene)-pyrrolinyl, (C₁₋₃alkylene)-piperidinyl, (C₁₋₃ alkylene)-morpholinyl, (C₁₋₃alkylene)-piperazinyl, (C₁₋₃ alkylene)-thiazolinyl, (C₁₋₃alkylene)-azepanyl, (C₁₋₃ alkylene)-diazepanyl, NO₂, SH, S—C₁₋₆ alkyl,OH, O—C₁₋₆ alkyl, O—C₁₋₆ alkyl-OH, C(═O)C₁₋₆ alkyl, NHSO₂C₁₋₆ alkyl,NHCOC₁₋₆ alkyl, CO₂H, CH₂SO₂ phenyl, CO₂—C₁₋₆ alkyl, OCF₃, CF₃,—O—CH₂—O—, —O—CH₂—CH₂—O—, —O—C(CH₃)₂—CH₂—, unsubstituted C₁₋₆ alkyl,pyrrolidinyl, imidazolyl, benzyloxy, phenoxy, phenyl, naphthyl,pyridinyl, —C₁₋₃ alkylene-aryl¹, benzyl, thienyl, furyl, wherein aryl¹denotes phenyl, thiazolyl, thienyl or pyridinyl, at one or differentatoms, wherein the aforementioned substituents—unless otherwisespecified—can themselves be substituted with the cited substituents. Thepolysubstitution of aryl and heteroaryl can be performed with identicalor different substituents. Preferred substituents for aryl andheteroaryl can be selected from the group consisting of —O—C₁₋₃ alkyl,unsubstituted C₁₋₆ alkyl, F, Cl, Br, I, CN, CF₃, OCF₃, OH, SH, —CH₂azetidinyl, —CH₂ pyrrolidinyl, —CH₂ piperidinyl, —CH₂ piperazinyl, —CH₂morpholinyl, phenyl, naphthyl, thiazolyl, thienyl and pyridinyl, inparticular from the group consisting of F, Cl, CN, CF₃, CH₃; OCH₃, OCF₃and —CH₂ azetidinyl.

In the chemical structural formulas which are used here to describe thecompounds according to the invention, the symbol

is also used to describe one or more substitution models, wherein unlikethe representation of a bond to a specific atom, this group is not boundto a specific atom within the chemical structural formula (by way ofexample R^(a) here represents a substituent R having a numberrepresented by the variable “a”). This can be explained by way ofexample by reference to the group

from the foregoing formula (III). The definition for R²⁷ indicates thatR²⁷ can denote 0 to 4 substituents. Thus R²⁷ can be absent, or 1, 2, 3or 4 of the hydrogen atoms attached to carbon atoms of the substructurerepresented by the formula (III) can be replaced by one of thesubstituents provided in the definition of R²⁷, wherein each of thesubstituents can be selected independently, in other words they can havedifferent meanings, and hydrogen atoms attached to carbon atoms can bereplaced at one or more carbon atoms. As explained in the definition ofR²⁷, two of the substituents R²⁷ can also together represent a C₁₋₃alkylene bridge or an anellated aryl or heteroaryl (also referred to asa fused aryl or heteroaryl or anellated/fused aryl or heteroaryl group),such that R²⁷ in formula (III) also has the meanings shown below by wayof example, in which R²⁷ denotes two substituents at different carbonatoms and in the second example the variable u denotes 1:

In the context of the present invention, the symbol

used in formulas represents a linking of a respective group to thehigher-order general structure.

Persons skilled in the art understand that identical substituents usedfor the definition of different substituents are mutually independent.

Within the meaning of this invention the term “physiologicallycompatible salt” is understood to mean salts of the compounds accordingto the invention with inorganic or organic acids which arephysiologically compatible, particularly when used in humans and/ormammals. Examples of suitable acids include hydrochloric acid,hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid,acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid,fumaric acid, maleic acid, lactic acid, citric acid, glutamic acid,1,1-dioxo-1,2-dihydro1λ⁶-benzo[d]isothiazol-3-one (saccharinic acid),monomethylsebacic acid, 5-oxoproline, hexane-1-sulfonic acid, nicotinicacid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid,α-lipoic acid, acetylglycine, hippuric acid, phosphoric acid and/oraspartic acid. The salts of hydrochloric acid (hydrochlorides) and ofcitric acid (citrates) are particularly preferred.

Within the scope of this invention the term “isolated” used withreference to a stereoisomer (i.e., an enantiomer or diasteromer) meansthat the stereoisomer is substantially completely separated from theopposite stereoisomer, but not necessarily from other substances.

In preferred embodiments of the compounds according to the inventionaccording to the formula (I) T, R²⁰⁰ and R²¹⁰ are selected such that theformula I assumes one of the formulas (Ia), (Ib) or (Ic)

wherein the various groups, variables and indices have the meaningsdescribed herein in connection with the compounds according to theinvention and the preferred embodiments thereof. The formula (I) can inparticular assume the formula (Ia).

In likewise preferred embodiments of the compounds according to theinvention x denotes 0, such that the radical D1 assumes the followingform D1′:

In further preferred embodiments of the compounds according to theinvention D denotes a group selected from the group consisting of

wherein

-   R³⁰⁰ denotes 0, 1, 2, 3 or 4 substituents each independently    selected from the group consisting of F, Cl, Br, I, —CF₃, —O—CF₃,    C₁₋₄ alkyl and O—C₁₋₄ alkyl;-   R³¹⁰ denotes 0, 1, 2 or 3 substituents each independently selected    from the group consisting of F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄ alkyl    and O—C₁₋₄ alkyl;-   R³²⁰ denotes a substituent selected from the group consisting of H,    F, Cl, Br, I, —CF₃, —O—CF₃ and C₁₋₄ alkyl;-   R³³⁰ denotes a substituent selected from the group consisting of H,    C₁₋₄ alkyl, aryl, —CH₂ aryl and heteroaryl;-   r1 denotes 1 or 2, and-   r2 denotes 1 or 2.

In likewise preferred embodiments of the compounds according to theinvention D denotes a group selected from the group consisting of

wherein

-   R³⁰⁰ denotes a substituent selected from the group consisting of F,    Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄ alkyl and O—C₁₋₄ alkyl;-   R³¹⁰ denotes a substituent selected from the group consisting of F,    Cl, Br, I, —CF₃, —O—CF₃, C₁₋₄ alkyl and O—C₁₋₄ alkyl;-   R³²⁰ denotes a substituent selected from the group consisting of H,    F, Cl, Br, I, —CF₃, —O—CF₃ and C₁₋₄ alkyl, and-   R³³⁰ denotes a substituent selected from the group consisting of H,    C₁₋₄ alkyl, aryl, —CH₂ aryl and heteroaryl.

In further preferred embodiments of the compounds according to theinvention D denotes a group selected from the group consisting of

In likewise preferred embodiments of the compounds according to theinvention y denotes 0, such that the group D2 assumes the following formD2′:

In the compounds according to the invention R³ preferably denotesphenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl(benzothienyl); benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl,thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl,imidazothiazolyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl(dibenzothienyl) or a phenyl or naphthyl bound via a C₁₋₃ alkylenegroup, particularly preferably for phenyl, naphthyl, chromanyl,benzothiophenyl (benzothienyl), benzooxadiazolyl, thienyl, pyridinyl,imidazothiazolyl, dibenzofuranyl or a phenyl bound via a C₁₋₃ alkylenegroup, most particularly preferably phenyl, naphthyl, chromanyl,benzothiophenyl (benzothienyl) or a phenyl bound via a C_(1 or 2)alkylene group, wherein the aforementioned aryl or heteroaryl groups mayeach be unsubstituted or mono- or polysubstituted, identically ordifferently, wherein the substituents are each independently selected inparticular from the group consisting of —O—C₁₋₃ alkyl, C₁₋₆ alkyl, F,Cl, Br, I, CF₃, OCF₃, OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyland pyridinyl and wherein the aforementioned alkylene groups are eachunsubstituted or mono- or polysubstituted, identically or differently,wherein the substituents are each independently selected in particularfrom the group consisting of —O—C₁₋₃ alkyl, F, Cl, Br, I, CF₃, OCF₃, OH,SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl.

R³ can in particular denote phenyl or naphthyl, wherein the phenyl ornaphthyl may be unsubstituted or mono- or polysubstituted, for exampledi-, tri-, tetra- or pentasubstituted, with identical or differentsubstituents selected from the group consisting of methyl, methoxy, CF₃,OCF₃, F and Cl.

In likewise preferred embodiments of the compounds according to theinvention R³ is selected from the group consisting of4-methoxy-2,3,6-trimethylphenyl, 4-methoxy-2,6-dimethylphenyl,4-methoxy-2,3,5-trimethylphenyl, 2,4,6-trimethylphenyl,2-chloro-6-methylphenyl, 2,4,6-trichlorophenyl,1,3-dichloro-5-trifluoromethylphenyl,2-chloro-6-(trifluoromethyl)phenyl, 2,6-dichloro-4-methoxyphenyl,2,6-dichloro-4-trifluoromethyl, 2-methylnaphthyl, 2-chloronaphthyl,2-fluoronaphthyl, 2-chloro-4-(trifluoromethoxy)phenyl,4-chloro-2,5-dimethylphenyl, 2-chloro-6-methylphenyl,2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl,2,4,5-trichlorophenyl, 2,4,6-trichlorophenyl, 2-(trifluoromethyl)phenyl,3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 1-naphthyl and2-naphthyl.

In particular R³ can denote 4-methoxy-2,6-dimethylphenyl,4-chloro-2,5-dimethylphenyl, 1-naphthyl or 2-(trifluoromethyl)phenyl.

In the compounds according to the invention R⁴ can in particular denotea substituent selected from the group consisting of H, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl andcyclopropyl. R⁴ particularly preferably denotes H.

In likewise preferred embodiments of the compounds according to theinvention q denotes 1 or 2.

Likewise preferred embodiments of the compounds according to theinvention are those in which R⁸ denotes H; C₁₋₆ alkyl, in particularmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl ortert-butyl; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, —CH₂CF₃,phenyl, benzyl, phenylethyl, phenylpropyl, or cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl bound via a C₁₋₃ alkylene group, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents. In particular R⁸ can denote H, methyl, ethyl, isopropyl orcyclopropyl.

Likewise preferred embodiments of the compounds according to theinvention are those in which R^(9a) and R^(9b) each each independentlydenote H; F; methyl; ethyl, isopropyl, CF₃, methoxy; cyclopropyl;phenyl; benzyl, phenylethyl, C₁₋₃ alkylene-cyclopropyl, C₁₋₃alkylene-cyclobutyl, C₁₋₃ alkylene-cyclopentyl, C₁₋₃ alkylene-cyclohexylor C₁₋₃ alkylene-CF₃, each unsubstituted or mono- or polysubstitutedwith identical or different substituents. In particular R^(9a) andR^(9b) each denote H.

Likewise preferred embodiments of the compounds according to theinvention are those in which the foregoing formula (II) assumes thefollowing substructure (IIa):

Likewise preferred embodiments of the compounds according to theinvention are those in which the foregoing formula (III) assumes one ofthe following substructures (IIIa) or (IIIb):

Likewise preferred embodiments of the compounds according to theinvention are those in which the substructure according to the formula(IIa) shown above assumes the following substructure (IIb):

wherein in certain embodiments of these compounds according to theinvention R⁸ can denote H or C₁₋₆ alkyl, in each case unsubstituted ormono- or polysubstituted with identical or different substituents, andR^(9a) and R^(9b) each denote H.

Likewise preferred embodiments of the compounds according to theinvention are those in which the substructures according to formulas(IIIa) and (IIIb) shown above assume one of the following substructures(IIIc), (IIId), (IIIe) or (IIIf):

In certain embodiments of these compounds according to the invention sand t each denote 0.

Likewise preferred embodiments of the compounds according to theinvention are those in which

-   (a1) the substructure having formula (IIa) assumes the substructure    (IIIb) and s and t each denote 0; or-   (a2) the substructures having formulas (IIIa) and (IIIb) assume one    of the substructures (IIIc) or (IIId) and s and t each denote 0; or-   (a3) the substructures having formulas (IIIa) and (IIIb) assume one    of the substructures (IIIc) or (IIId) and two of the substituents    R²⁷ together form a C₁₋₃ alkylene bridge such that the cyclic    compound represented in substructure (IIIc) or (IIId) assumes a    bicyclically bridged form, and s and t each denote 0; or-   (a4) the substructures having formulas (IIIa) and (IIIb) assume one    of the substructures (IIIc), (IIId), (IIIe) or (IIIf), s denotes 1    and t denotes 0, 1, 2 or 3 and R⁸ denotes H, C₁₋₆ alkyl or C₃₋₆    cycloalkyl, in each case unsubstituted or mono- or polysubstituted    with identical or different substituents, and R^(9a) and R^(9b) each    independently denote H, C₁₋₆ alkyl or C₃₋₆ cycloalkyl.

Likewise preferred embodiments of the compounds according to theinvention are those in which

-   s and t each denote 0 and the formula (II) assumes the following    substructure (IIc)

wherein

-   c, d, e and f each independently denote 0, 1 or 2;-   X denotes CR^(14a)R^(14b), NR¹⁵ or O,-   Z denotes CR^(18a)R^(18b) or NR¹⁹, or-   if X denotes O and f denotes 0, then Z denotes ═(N(CR¹²⁶))—, wherein    the N atom is singly bonded to the O atom,-   R¹²⁶ denotes H, C₁₋₄ alkyl or an unsubstituted or mono- or    polysubstituted phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,    thiazolyl or thienyl optionally bound via a C₁₋₃ alkylene group,    wherein the substituents are preferably each independently selected    from the group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and    O—C₁₋₄ alkyl,-   R^(14a), R^(14b), R^(16a) and R^(16b) each independently denote H or    an unsubstituted or mono- or polysubstituted phenyl, pyridyl,    imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl optionally    bound via a C₁₋₃ alkylene group, wherein the substituents are    preferably each independently selected from the group consisting of    F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, and/or R^(16a)    and R^(16b) together denote ═O;-   R¹⁵ denotes H, C₁₋₄ alkyl or an unsubstituted or mono- or    polysubstituted phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,    thiazolyl or thienyl optionally bound via a C₁₋₃ alkylene group,    wherein the substituents are preferably selected from the group    consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl,-   R^(18a) denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl),    —N(C₁₋₆ alkyl)₂, unsubstituted or mono- or polysubstituted phenyl,    pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, or    an unsubstituted or mono- or polysubstituted phenyl, pyridyl,    imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl bound by an    —(O)₀₋₁—C₁₋₆ alkylene group; wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or-   R^(18a) denotes the radical according to the formula (IVa)

wherein

-   -   i denotes 0 or 1;    -   j denotes 0 or 1;    -   h and g, each independently, denote 0 or 1,    -   E denotes N or CH; with the proviso that if i denotes 1 and j        denotes 0 then E denotes CH,    -   G denotes CR^(37a)R^(37b) or NR³⁸;    -   wherein    -   R^(37a) and R^(37b) each independently denote H; F or C₁₋₄        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents,    -   R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl;

-   R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl, imidazolyl,    triazolyl, pyrimidyl, thiazolyl or thienyl, each unsubstituted or    mono- or polysubstituted with identical or different substituents;    phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or    thienyl bound via a C₁₋₆ alkylene group, each unsubstituted or mono-    or polysubstituted with identical or different substituents;    O-phenyl or O-pyridyl, each unsubstituted or mono- or    polysubstituted with identical or different substituents, phenyl,    pyridyl or thienyl bridged by C₁₋₆ alkylene-NH(C═O), each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl,

-   R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆    alkylene-NH(C₁₋₆ alkyl), C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl,    pyridyl, thienyl, thiazolyl, triazolyl, pyrimidinyl or imidazolyl;    each unsubstituted or mono- or polysubstituted with identical or    different substituents; or phenyl, pyridyl, thienyl, thiazolyl,    pyrimidinyl, triazolyl or imidazolyl bound via a C₁₋₆ alkylene    group; each unsubstituted or mono- or polysubstituted with identical    or different substituents, wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or a group according to the    formula (VIIIa)

wherein

-   -   w denotes 0 or 1;    -   n denotes 0 or 1;    -   m denotes 0 or 1;    -   M denotes CH or N, with the proviso that if w denotes 0 then M        denotes CH;    -   L denotes CR^(44a)R^(44b) or NR⁴⁵;    -   wherein    -   R^(44a) and R^(44b) each independently denote H; F or C₁₋₆        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents; and    -   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl.

Other preferred embodiments of the compounds according to the inventionare those in which

-   s and t each denote 0 and the formula (III) assumes one of the    substructures (IIIc′) or (IIId′)

wherein u and v each independently denote 0, 1 or 2,

-   R^(18a) denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl),    —N(C₁₋₆ alkyl)₂, unsubstituted or mono- or polysubstituted phenyl,    pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, or    an unsubstituted or mono- or polysubstituted phenyl, pyridyl,    imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl bound by an    —(O)₀₋₁—C₁₋₆ alkylene group; wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or-   R^(18a) denotes the radical according to the formula (IVa)

wherein

-   -   i denotes 0 or 1;    -   j denotes 0 or 1;    -   h and g, each independently, denote 0 or 1,    -   E denotes N or CH; with the proviso that if i denotes 1 and j        denotes 0 then E denotes CH,    -   G denotes CR^(37a)R^(37b) or NR³⁸;    -   wherein    -   R^(37a) and R^(37b) each independently denote H; F or C₁₋₄        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents,    -   R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl; or

-   R^(18a) denotes the following radical:

-   R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl, imidazolyl,    triazolyl, pyrimidyl, thiazolyl or thienyl, each unsubstituted or    mono- or polysubstituted with identical or different substituents;    phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or    thienyl bound via a C₁₋₆ alkylene group, each unsubstituted or mono-    or polysubstituted with identical or different substituents;    O-phenyl or O-pyridyl, each unsubstituted or mono- or    polysubstituted with identical or different substituents, phenyl,    pyridyl or thienyl bridged by C₁₋₆ alkylene-NH(C═O), each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl,-   R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆    alkylene-NH(C₁₋₆ alkyl), C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl,    pyridyl, thienyl, thiazolyl, triazolyl, pyrimidinyl or imidazolyl;    each unsubstituted or mono- or polysubstituted with identical or    different substituents; or phenyl, pyridyl, thienyl, thiazolyl,    pyrimidinyl, triazolyl or imidazolyl bound via a C₁₋₆ alkylene    group; each unsubstituted or mono- or polysubstituted with identical    or different substituents, wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or a group according to the    formula (VIIIa)

wherein

-   w denotes 0 or 1;-   n denotes 0 or 1;-   m denotes 0 or 1;-   M denotes CH or N, with the proviso that if w denotes 0, then M    denotes CH;-   L denotes CR^(44a)R^(44b) or NR⁴⁵; wherein    -   R^(44a) and R^(44b) each independently denote H; F or C₁₋₆        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents; and    -   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or pyridyl.

Preferred embodiments of the compounds according to the invention arealso those in which

-   s and t each denote 0, and the formula (III) assumes one of the    following substructures (A) to (H)

and wherein

-   R^(18a) denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl),    —N(C₁₋₆ alkyl)₂, unsubstituted or mono- or polysubstituted phenyl,    pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, or    an unsubstituted or mono- or polysubstituted phenyl, pyridyl,    imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl bound by an    —(O)₀₋₁—C₁₋₆ alkylene group; wherein the substituents are preferably    each each independently selected from the group consisting of F, Cl,    CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or-   R^(18a) denotes a group according to the formula (IVa)

wherein

-   I denotes 0 or 1;-   J denotes 0 or 1;-   h and g, each independently, denote 0 or 1,-   E denotes N or CH; with the proviso that if i denotes 1 and j    denotes 0, then E denotes CH;-   G denotes CR^(37a)R^(37b) or NR³⁸; wherein    -   R^(37a) and R^(37b) each independently denote H; F or C₁₋₄        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents,    -   R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl;-   R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl, imidazolyl,    triazolyl, pyrimidyl, thiazolyl or thienyl, each unsubstituted or    mono- or polysubstituted with identical or different substituents;    phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or    thienyl bound via a C₁₋₆ alkylene group, each unsubstituted or mono-    or polysubstituted with identical or different substituents;    O-phenyl or O-pyridyl, each unsubstituted or mono- or    polysubstituted with identical or different substituents, phenyl,    pyridyl or thienyl bridged by C₁₋₆ alkylene-NH(C═O), each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl;-   R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆    alkylene-NH(C₁₋₆ alkyl), C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl,    pyridyl, thienyl, thiazolyl, triazolyl, pyrimidinyl or imidazolyl;    each unsubstituted or mono- or polysubstituted with identical or    different substituents; or phenyl, pyridyl, thienyl, thiazolyl,    pyrimidinyl, triazolyl or imidazolyl bound via a C₁₋₆ alkylene    group; each unsubstituted or mono- or polysubstituted with identical    or different substituents, wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or a group according to the    formula (VIIIa)

wherein

-   w denotes 0 or 1;-   n denotes 0 or 1;-   m denotes 0 or 1;-   M denotes CH or N, with the proviso that if w denotes 0 then M    denotes CH;-   L denotes CR^(44a)R^(44b) or NR⁴⁵; wherein    -   R^(44a) and R^(44b) each independently denote H; F or C₁₋₆        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents; and    -   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl.

Preferred embodiments of the compounds according to the invention arealso those in which

-   s denotes 1,-   t denotes 0, 1, 2 or 3,-   R⁸ denotes H, C₁₋₄ alkyl or C₃₋₆ cycloalkyl-   R^(9a) and R^(9b) each independently denote H, C₁₋₄ alkyl or C₃₋₆    cycloalkyl, and preferably both denote H;-   the formula (III) assumes one of the following substructures    (IIIc′), (IIId′), (IIIe′) or (IIIf′)

wherein

-   u and v each independently denote 0, 1 or 2,-   R^(18a) denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl),    —N(C₁₋₆ alkyl)₂, unsubstituted or mono- or polysubstituted phenyl,    pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, or    unsubstituted or mono- or polysubstituted phenyl, pyridyl,    imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl bound by an    —(O)₀₋₁—C₁₋₆ alkylene group; wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or-   R^(18a) denotes a group according to the formula (IVa)

wherein

-   I denotes 0 or 1;-   J denotes 0 or 1;-   h and g each independently denote 0 or 1,-   E denotes N or CH; with the proviso that if i denotes 1 and j    denotes 0, then E denotes CH,-   G denotes CR^(37a)R^(37b) or NR³⁸; wherein    -   R^(37a) and R^(37b) each independently denote H; F or C₁₋₄        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents,    -   R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl;-   R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl, imidazolyl,    triazolyl, pyrimidyl, thiazolyl or thienyl, each unsubstituted or    mono- or polysubstituted with identical or different substituents;    phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or    thienyl bound via a C₁₋₆ alkylene group, each unsubstituted or mono-    or polysubstituted with identical or different substituents;    O-phenyl or O-pyridyl, each unsubstituted or mono- or    polysubstituted with identical or different substituents, phenyl,    pyridyl or thienyl bridged by C₁₋₆ alkylene-NH(C═O), each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl,-   R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆    alkylene-NH(C₁₋₆ alkyl), C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl,    pyridyl, thienyl, thiazolyl, triazolyl, pyrimidinyl or imidazolyl;    each unsubstituted or mono- or polysubstituted with identical or    different substituents; or phenyl, pyridyl, thienyl, thiazolyl,    pyrimidinyl, triazolyl or imidazolyl bound via a C₁₋₆ alkylene    group; each unsubstituted or mono- or polysubstituted with identical    or different substituents, wherein the substituents are preferably    each independently selected from the group consisting of F, Cl, CF₃,    C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl,    or a group according to the formula (VIIIa)

wherein

w denotes 0 or 1;

n denotes 0 or 1;

m denotes 0 or 1;

M denotes CH or N; with the proviso that if w denotes 0, then M denotesCH;

L denotes CR^(44a)R^(44b) or NR⁴⁵; wherein

-   -   R^(44a) and R^(44b) each independently denote H; F or C₁₋₆        alkyl, each unsubstituted or mono- or polysubstituted with        identical or different substituents;    -   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl.

Other preferred embodiments of the compounds according to the inventionare compounds in which the substructure according to formula II shownabove assumes one of the following substructures SP:

wherein

-   R¹³ denotes 1 or 2 groups selected from H and phenyl, unsubstituted    or mono- or polysubstituted with identical or different    substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl; and/or-   two substituents R¹³ together form ═O; and/or-   two adjacent substituents R¹³ together form an anellated aryl or    heteroaryl, in particular a benzo group, each unsubstituted or mono-    or polysubstituted with identical or different substituents, wherein    the substituents are preferably each independently selected from the    group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄    alkyl;-   R¹⁵ denotes H; C₁₋₆ alkyl; C₃₋₈ cycloalkyl or unsubstituted or    identically or differently mono- or polysubstituted phenyl or    pyridyl or a phenyl or pyridyl bound via a C₁₋₆ alkylene group, each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl;-   R^(16a) denotes H, C₁₋₆ alkyl, or phenyl or pyridyl, each    unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl;-   R^(18a) denotes H; C₁₋₆ alkyl; C₃₋₈ cycloalkyl, N(C₁₋₆ alkyl)₂;    NH(C₁₋₆ alkyl), azetidinyl; pyrrolidinyl, piperidinyl, 4-(C₁₋₆    alkyl)-piperazinyl; phenyl or pyridyl, each unsubstituted or mono-    or polysubstituted with identical or different substituents; or    N(C₁₋₆ alkyl)₂; NH(C₁₋₆ alkyl), azetidinyl; pyrrolidinyl,    piperidinyl, 4-(C₁₋₆ alkyl)-piperazinyl; phenyl, imidazolyl,    triazolyl or pyridyl bound by an —(O)_(0/1)—C₁₋₆ alkylene group,    each unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents of C₁₋₆ alkyl; C₃₋₈    cycloalkyl, azetidinyl; pyrrolidinyl, piperidinyl and 4-(C₁₋₆    alkyl)-piperazinyl are preferably each independently selected from    the group consisting of F, Cl, CF₃, ═O, C₁₋₄ alkyl, OCF₃, OH and    O—C₁₋₄ alkyl, and wherein the substituents of phenyl, imidazolyl,    triazolyl or pyridyl are preferably each independently selected from    the group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄    alkyl;-   R^(18b) denotes H; OH; C₁₋₆ alkyl; phenyl or pyridyl, each    unsubstituted or mono- or polysubstituted with identical or    different substituents, or phenyl or pyridyl bound via a C₁₋₆    alkylene group, each unsubstituted or mono- or polysubstituted with    identical or different substituents; wherein the substituents of    phenyl and pyridyl are preferably each independently selected from    the group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄    alkyl;-   R¹⁹ denotes H; C₁₋₆ alkyl; C₃₋₈ cycloalkyl, phenyl, pyridyl,    thienyl, imidazolyl, thiazolyl or triazolyl, each unsubstituted or    mono- or polysubstituted with identical or different substituents,    or phenyl or pyridyl bound via a C₁₋₆ alkylene group or (C═O) group,    each unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents of phenyl, pyridyl,    thienyl, imidazolyl, thiazolyl and triazolyl are preferably each    independently selected from the group consisting of F, Cl, CF₃, C₁₋₄    alkyl, OCF₃, OH and O—C₁₋₄ alkyl;-   R¹²⁰ denotes H; F; Cl; OH; OCH₃, O—CF₃, C₁₋₆ alkyl; CF₃, phenyl,    unsubstituted or mono- or polysubstituted, wherein the substituents    of phenyl are preferably each independently selected from the group    consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl;-   R¹²⁶ denotes H; C₁₋₆ alkyl; C₃₋₆ cycloalkyl; phenyl or pyridyl; or    C₃₋₆ cycloalkyl, phenyl or pyridyl bound via a C₁₋₃ alkylene group,    each unsubstituted or mono- or polysubstituted with identical or    different substituents, wherein the substituents of phenyl and    pyridyl are preferably each independently selected from the group    consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl.

Of the substructures SP, substructures SP1, SP2, SP5, SP10, SP23, SP32and SP26 are preferably present in the compounds according to theinvention.

Other preferred embodiments of the compounds according to the inventionare compounds in which the following substructure (B) in the formula Ishown above

is selected from one of the following substructures B.1. to B.57.

wherein

-   h=0 or 1;-   g=0 or 1;-   m=0 or 1;-   n=0 or 1;-   o=0, 1, 2 or 3;-   r=1, 2 or 3, in particular 1 or 2;-   s=0 or 1;-   t=0, 1, 2 or 3, in particular 0, 1 or 2, with the proviso that if s    denotes 0, then t likewise denotes 0;-   M¹, M² and M³ each denote N or CH, wherein one variable out of M¹,    M² and M³ denotes N, and the other two each denote CH;-   R⁸ denotes H; C₁₋₆ alkyl, in particular methyl, ethyl, n-propyl,    isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl; C₃₋₆    cycloalkyl, in particular cyclopropyl, each unsubstituted or mono-    or polysubstituted with identical or different substituents;-   R¹⁹ denotes H; C₁₋₆ alkyl, in particular methyl, ethyl, n-propyl,    isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl; C₃₋₆    cycloalkyl, in particular cyclopropyl; each unsubstituted or mono-    or polysubstituted with identical or different substituents;-   R³⁴ and R³⁵ are preferably each independently methyl or ethyl or    together with the N-atom linking them form an azetidinyl;    pyrrolidinyl, piperidinyl or 4-(C₁₋₆ alkyl)-piperazinyl group, each    unsubstituted or mono- or polysubstituted with identical or    different substituents;-   R³⁸ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or pyridyl;-   R³⁹ denotes H; C₁₋₆ alkyl, in particular methyl, ethyl, n-propyl,    isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl; C₃₋₆    cycloalkyl, in particular cyclopropyl, each unsubstituted or mono-    or polysubstituted with identical or different substituents;-   R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or pyridyl; and-   R¹⁹⁰ represents 0 to 4 substituents, which are each independently    selected from F, Cl, O—CF₃, CF₃ or CN.

Of the substructures B, substructures B.1., B.3., B.4., B.10., B.11.,B.44., B.8., B.17., B.15., B.54., B.13., B.19., B.20., B.45., B.21.,B.49., B.24., B.25., B.27., B.29., B.47., B.55., B.37., B.36., B.57.,B.30., B.32., B.34., B.48. and B.50. are preferably present in thecompounds according to the invention.

In substructures B.1., B.3., B.4., B.29., B.44. and B.54., preferably M¹denotes N and M² and M³ each denote CH. In substructure B.8. preferablyo denotes 1 and R¹⁹⁰ denotes H. In substructure B.17. preferably R¹⁹denotes H. In substructure B.15. preferably R¹⁹ denotes CH₃ and R¹⁹⁰denotes F in the 4-position. In substructure B.13. preferably o denotes0 or 1, and R¹⁹⁰ denotes H or F in the 4-position. In substructure B.30.preferably R⁸ denotes H, s denotes 1, t denotes 1 or 2, M¹ denotes N andM² and M³ each denote CH. In substructure B.32. preferably R⁸ denotesCH₃, S denotes 1, t denotes 3, R³⁴ and R³⁵ each denote CH₃ and R¹⁹⁰denotes H. In substructure B.34. preferably R⁸ denotes CH₃, s denotes 1,t denotes 2 or 3, R³⁴ and R³⁵ each denote CH₃ and R¹⁹⁰ denotes H. Insubstructure B.48. preferably R⁸ denotes H, s denotes 1, t denotes 0,R³⁴ and R³⁵ together with the nitrogen atom linking them form anazetidinyl group, and R¹⁹⁰ denotes H. In substructure B.50. preferablyR⁸ denotes H, s denotes 1, t denotes 3 and R³⁸ denotes ethyl. Insubstructure B.27. preferably o denotes 2, and g and h each denote 1. Insubstructure B.47. preferably o denotes 0, h and g each denote 1, andR³⁸ denotes CH₃. In substructure B.37. preferably M¹ denotes N, M² andM³ each denote CH, r denotes 2, and R³⁴ and R³⁵ together with thenitrogen atom linking them form a pyrrolidinyl group. In substructuresB.56. and B.57. preferably R¹⁹⁰ denotes H, and R³⁴ and R³⁵ each denoteCH₃. In substructure B.19. preferably o denotes 0 or 1, n and m eachdenote 1, and R⁴⁵ denotes CH₃. In substructure B.21. preferably odenotes 0, and R¹⁹⁹ denotes F in the 4-position. In substructure B.49.preferably o denotes 3, and R³⁴ and R³⁵ each denote CH₃. In substructureB.20. preferably o denotes 0, M¹ denotes N, and M² and M³ each denoteCH. In substructure B.24. preferably o denotes 1, and R¹⁹⁰ denotes F inthe 4-position. In substructure B.25. preferably o denotes 1, M¹ denotesN, and M² and M³ each denote CH.

Further embodiments of the compounds according to the invention arethose which are represented by the following formulas C1 to C14:

wherein the various groups, variables and indices have the meaningsdescribed above in connection with the compounds according to theinvention and the preferred embodiments thereof.

In a further preferred embodiment of the present invention thesubstituted compounds according to the invention can be selected fromthe group consisting of

No. Compound G-014-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G-024-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G-034-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyridin-4-yloxy-piperidin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G-044-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(1-oxo-4-phenyl-2,4,8-triazaspiro[4.5]decan-8-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide G-05 4-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide G-064-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amideG-077-Chloro-2-[1-[3-oxo-3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G-087-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G-107-Chloro-2-(1-(3-oxo-3-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)propyl)-1H-indol-7-yl)isoindolin-1-one G-117-Chloro-2-(1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)isoindolin-1-one G-127-Chloro-2-(1-(2-oxo-2-(8-(pyridin-4-yl)-2,8-diazaspiro[4.5]decan-2-yl)ethyl)-1H-indol-6-yl)isoindolin-1-one G-134-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(3-(pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-14 4-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(8-(pyridin-4-yl)-2,8-diazaspiro[4.5]decan-2-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-157-Chloro-2-(1-(2-oxo-2-(3-(pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)ethyl)-1H-indol-6-yl)isoindolin-1-one G-164-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(3-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidin-1-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acid amide G-174-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(7-(pyridin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-18N-(1-(2-(9-(azetidin-1-yl)-3-azaspiro[5.5]undecan-3-yl)-2-oxoethyl)-1H-indol-7-yl)-4-methoxy-2,6-dimethylbenzenesulfonic acid amide G-197-Chloro-2-(1-(2-oxo-2-(9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-6-yl)isoindolin-1-one G-207-Chloro-2-(1-(2-(9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecan-3-yl)-2-oxoethyl)-1H-indol-6-yl)isoindolin-1-one G-212-(1-(2-(9-(Azetidin-1-yl)-3-azaspiro[5.5]undecan-3-yl)-2-oxoethyl)-1H-indol-6-yl)-7-chloroisoindolin-1-one G-224-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-23 8-Chloro-4-methyl-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one G-244-Methoxy-2,6-dimethyl-N-[[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-7-yl]-methyl]-benzenesulfonic acid amide G-267-Methyl-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G-275-Methyl-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-1,2-dihydro-pyrrolo[2,1-e]imidazol-3-one G-3110-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one G-338-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one G_CC-14-Methoxy-2,6-dimethyl-N-[1-[2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-24-Methoxy-2,6-dimethyl-N-[1-[2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-34-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyrimidin-2-yl-piperazin-1-yl)-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-44-Methoxy-2,6-dimethyl-N-[1-[2-[4-[(1-methyl-piperdin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amideG_CC-5N-[1-[2-[4-(4-fluorophenyl)-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-64-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyrimidin-2-yl-piperazin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-74-Methoxy-2,6-dimethyl-N-[1-[2-[4-[(1-methyl-piperdin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amideG_CC-84-Chloro-2,5-dimethyl-N-[1-[2-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-92-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[(1-pyridin-4-yl-piperidin-4-yl)-methyl]-acetamide G_CC-10N-[1-[2-(3-Benzyl-3,7-diazaspiro[4.4]nonan-7-yl)-2-oxo-ethyl]-1H-indol-6-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-11N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-12N-[1-[2-[3-(4-Fluorophenyl)-4-oxo-3,8-diazaspiro[4.5]decan-8-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amideG_CC-13N-[1-[2-(3-Benzyl-3,7-diazaspiro[4.4]nonan-7-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-14N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-152-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[3-(4-dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-N-methyl-acetamideG_CC-16N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-N-methyl-2-[7-[(naphthalen-1-ylsulfonyl)amino]-1H-indol-1-yl]-acetamide G_CC-17N-[4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamide G_CC-18N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide G_CC-19N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamideG_CC-20N-[1-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-212-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-22N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]- propionamideG_CC-233-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-242-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-25N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-N-methyl-2-[7-[(naphthalen-1-ylsulfonyl)amino]-1H-indol-1-yl]-acetamide G_CC-262-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[3-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-N-methyl-acetamide G_CC-272-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-acetamideG_CC-282-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-29N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide G_CC-30N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamideG_CC-31N-[1-[2-[1-(4-Fluorophenyl)-3-methyl-4-oxo-3,8-diazaspiro[4.5]decan-8-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonicacid amide G_CC-32N-[1-[2-(3-Benzyl-4-oxo-3,8-diazaspiro[4.5]decan-8-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-33N-[1-[2-[2-[(4-Fluorophenyl)-methyl]-2,5-diazabicyclo[2.2.1]heptan-5-yl]-2-oxo-ethyl]-1H-indol-6-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acidamide G_CC-344-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[2-(pyridin-4-yl-methyl)-2,5-diazabicyclo[2.2.1]heptan-5-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonicacid amide G_CC-354-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-6-yl]-benzenesulfonic acidamide G_CC-36 4-Chloro-2,5-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-6-yl]-benzenesulfonic acidamide G_CC-37N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-6-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-38N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-naphthalene-1-sulfonic acid amide G_CC-394-Chloro-2,5-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide G_CC-404-Methoxy-2,6-dimethyl-N-[1-[3-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-414-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-424-Methoxy-2,6-dimethyl-N-[1-[3-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-434-Methoxy-2,6-dimethyl-N-[1-[3-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amideG_CC-44N-[1-[3-[4-(3-Dimethylamino-propyl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-45N-[1-[3-(4-Hydroxy-4-pyridin-2-yl-piperidin-1-yl)-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-46N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide G_CC-473-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-48N-[1-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-49N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide G_CC-50N-[4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-51N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamideG_CC-52N-[1-[3-Oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-7-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-53N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-544-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-7-yl]-benzenesulfonic acidamide G_CC-56N-[3-(4-Ethyl-piperazin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-574-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amideG_CC-594-Chloro-2,5-dimethyl-N-[1-[3-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-604-Chloro-2,5-dimethyl-N-[1-[3-oxo-3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-614-Chloro-2,5-dimethyl-N-[1-[3-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-624-Chloro-2,5-dimethyl-N-[1-[3-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amideG_CC-637-Chloro-2-[1-[3-oxo-3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G_CC-647-Chloro-2-[1-[3-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-3-oxo-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G_CC-654-Chloro-2,5-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-6-yl]-benzenesulfonic acidamide G_CC-668-[3-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-propanoyl]-3-[(4-fluorophenyl)-methyl]-3,8-diazaspiro[4.5]decan-4-oneG_CC-677-Chloro-2-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G_CC-687-Chloro-2-[1-[3-oxo-3-(4-pyridin-4-yloxy-piperidin-1-yl)-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G_CC-697-Chloro-2-[1-[3-(4-hydroxy-4-pyridin-3-yl-piperidin-1-yl)-3-oxo-propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one G_CC-703-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-713-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-723-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-733-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-propionamideG_CC-743-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-propionamideG_CC-762-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-acetamide G_CC-77N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-81N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide G_CC-84N-[1-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acidamide G_CC-882-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-acetamide G_CC-914-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro-[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amideG_CC-924-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyridin-4-yloxy-piperidin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-95N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-99N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide G_CC-102N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide G_CC-1032-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-1067-Chloro-2-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-7-yl]-2,3-dihydro-isoindol-1-one G_CC-108N-[[1-[2-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetyl]-4-(4-methyl-piperazin-1-yl)-piperidin-4-yl]-methyl]-pyridine-4-carboxylic acid amide G_CC-1112-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[(1-pyridin-4-yl-piperidin-4-yl)-methyl]-acetamide G_CC-1132-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[2-[4-(3-fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-N-methyl-acetamide G_CC-1163-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-propionamideG_CC-117N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide G_CC-1193-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-propionamide G_CC-1204-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amideG_CC-1233-[7-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[(1-pyridin-4-yl-piperidin-4-yl)-methyl]-propionamide G_CC-1273-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-phenyl-cyclohexyl)-ethyl]-N-methyl-propionamide G_CC-1287-Chloro-2-[1-[2-[4-(3-fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-oneG_CC-1382-[6-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-acetamide G_CC-1394-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(pyridin-3-carbonyl)-piperazin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amideoptionally in the form of an isolated enantiomer or an isolateddiastereomer, the racemate, the enantiomers, the diastereomers, mixturesof enantiomers or diastereomers, each in the form of their bases and/orphysiologically compatible salts, in particular hydrochloride salts.

The numbering of the individual embodiments of the compounds accordingto the invention used above is retained in the following explanations ofthe present invention, particularly in the description of the examples.

According to one aspect of the present invention the compounds accordingto the invention preferably have an antagonistic action on the human B1Rreceptor or the B1R receptor of the rat. In a preferred embodiment ofthe invention the compounds according to the invention have anantagonistic action on both the human B1R receptor (hB1R) and on the B1Rreceptor of the rat (rB1R).

In a preferred embodiment of the present invention the compoundsaccording to the invention exhibit at least 15%, 25%, 50%, 70%, 80% or90% inhibition on the human B1R receptor and/or on the B1R receptor ofthe rat in the FLIPR assay at a concentration of 10 μM. Mostparticularly preferred are compounds which exhibit at least 70%, inparticular at least 80% and particularly preferably at least 90%inhibition on the human B1R receptor and on the B1R receptor of the ratat a concentration of 10 μM.

The agonistic or antagonistic action of substances can be quantified onthe bradykinin 1 receptor (B1R) of the human and rat species withectopically expressing cell lines (CHO K1 cells) and with the aid of aCa²⁺-sensitive dye (Fluo-4) using a fluorescent imaging plate reader(FLIPR). The indication in % activation is based on the Ca²⁺ signalafter addition of Lys-Des-Arg⁹ bradykinin (0.5 nM) or Des-Arg⁹bradykinin (100 nM). Antagonists lead to a suppression of the Ca²⁺influx following administration of the agonist. The % inhibition incomparison with the maximum achievable inhibition is indicated.

The substances according to the invention preferably act for example onthe B1R of relevance in connection with various diseases, such that theyare suitable as a pharmaceutical active ingredient in medicinalproducts.

The invention therefore also provides medicinal products containing atleast one compound according to the invention, optionally along withsuitable additives and/or auxiliary substances and/or optionally furtheractive ingredients.

The medicinal products according to the invention optionally contain, inaddition to at least one compound according to the invention, suitableadditives and/or auxiliary substances, including carrier materials,fillers, solvents, diluents, dyes and/or binders, and can beadministered as liquid dosage forms in the form of injection solutions,drops or juices, as semi-solid dosage forms in the form of granules,tablets, pellets, patches, capsules, plasters/spray plasters oraerosols. The choice of auxiliary substances, etc., and the amountsthereof to use depend on whether the medicinal product is to beadministered by oral, peroral, parenteral, intravenous, intraperitoneal,intradermal, intramuscular, nasal, buccal, rectal or topical means, forexample on the skin, mucous membranes or in the eyes. Preparations inthe form of tablets, pastilles, capsules, granules, drops, juices andsyrups are suitable for oral administration; solutions, suspensions,easily reconstitutable dry preparations and sprays are suitable forparenteral, topical and inhalative administration. Substituted indolecompounds according to the invention in a depot formulation, indissolved form or in a plaster, optionally with addition of agentspromoting skin penetration, are suitable preparations for percutaneousadministration. Preparation forms suitable for oral or percutaneousadministration can deliver the substituted indole compounds according tothe invention on a delayed release basis. The substituted indolecompounds according to the invention can also be used in parenterallong-term depot forms, such as implants or implanted pumps, for example.Other additional active ingredients known to the person skilled in theart can be added in principle to the medicinal products according to theinvention.

The amount of active ingredient to be administered to the patient variesaccording to the weight of the patient, the manner of administration,the indication and the severity of the illness. Generally 0.00005 to 50mg/kg, in particular 0.01 to 5 mg/kg, of at least one compound accordingto the invention are conventionally administered.

One form of the medicinal product contains a substituted indole compoundaccording to the invention optionally as an isolated diastereomer and/orenantiomer, as a racemate or as a non-equimolar or equimolar mixture ofdiastereomers and/or enantiomers.

B1R is involved in particular in the pain mechanism. The substitutedindole compounds according to the invention can accordingly be used inparticular for the preparation of a medicinal product for the treatmentof pain, in particular acute, visceral, neuropathic or chronic pain orinflammatory pain.

The invention therefore also provides the use of at least onesubstituted indole compound according to the invention to prepare amedicinal product for the treatment of pain, in particular acute,visceral, neuropathic or chronic pain. A particular embodiment of thepresent invention is the use of at least one of the substituted indolecompounds according to the invention to prepare a medicinal product forthe treatment of inflammatory pain.

The invention also provides the use of at least one substituted indolecompound according to the invention for the treatment of pain, inparticular acute, visceral, neuropathic or chronic pain or inflammatorypain.

The invention also provides the use of at least one substituted indolecompound according to the invention to prepare a medicinal product forthe treatment of diabetes, diseases of the respiratory tract, forexample bronchial asthma, allergies, COPD/chronic obstructive pulmonarydisease or cystic fibrosis; inflammatory bowel diseases, for exampleulcerative colitis or CD/Crohn's disease; neurological diseases, forexample multiple sclerosis or neurodegeneration; inflammations of theskin, for example atopic dermatitis, psoriasis or bacterial infections;rheumatic diseases, for example rheumatoid arthritis or osteoarthritis;septic shock; reperfusion syndrome, for example following heart attackor stroke; obesity; and as an angiogenesis inhibitor.

The invention also provides the use of at least one substituted indolecompound according to the invention for treating any of the foregoingindications.

In the above uses it may be preferable for a substituted indole compoundthat is used to be in the form of an isolated diastereomer and/orenantiomer, a racemate or a non-equimolar or equimolar mixture ofdiastereomers and/or enantiomers.

The invention also provides a process for treating, in particular one ofthe aforementioned indications, in a non-human mammal or human requiringtreatment of the corresponding indication, by administration of atherapeutically active dose of a substituted indole compound accordingto the invention or of a medicinal product according to the invention.

The invention also provides a process for treating pain, in particularone of the aforementioned forms of pain, in a non-human mammal or humanrequiring in particular treatment of pain, in particular of acute,visceral, neuropathic or chronic pain or inflammatory pain, byadministration of a therapeutically active dose of a substituted indolecompound according to the invention or of a medicinal product accordingto the invention.

The present invention also provides methods for preparing thesubstituted indole compounds according to the invention as listed in thedescription and in the examples.

General Method for Preparing the Indolamide Derivative G

In stage 1 sulfonyl chlorides having the formula (C), wherein R³ has themeaning given above, in at least one solvent, preferably selected fromthe group consisting of dichloromethane, acetonitrile, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanoland isopropanol, are reacted with amino acid esters (A), in the presenceof at least one inorganic base, preferably selected from the groupconsisting of potassium carbonate and caesium carbonate, or an organicbase, preferably selected from the group consisting of triethylamine,diisopropylethylamine and pyridine, and optionally with addition of4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, at temperatures ofpreferably −15° C. to 50° C., to form compounds having the formula (D).

In stage 2 compounds of formula (D) in at least one solvent, preferablyselected from the group consisting of water, methanol, ethanol,isopropanol, diethyl ether, tetrahydrofuran, toluene, acetonitrile,dimethyl formamide, dioxane and dimethyl sulfoxide, are reacted with aninorganic base, preferably selected from the group consisting of lithiumhydroxide, sodium hydroxide, potassium hydroxide, potassiumtert-butanolate, lithium propanethiolate and sodium phenyl selenolate,optionally with addition of HMPA or lithium chloride, or with a Lewisacid, preferably selected from the group consisting of trimethylsilylchloride, boron tribromide and aluminium trichloride, optionally withaddition of thiolene, sodium iodide or lithium chloride, at temperaturesof preferably 0° C. to 100° C., to form compounds of formula (E).

In stage 3 compounds of formula (E) in at least one solvent, preferablyselected from the group consisting of dichloromethane, acetonitrile,dimethyl formamide, diethyl ether, dioxane and tetrahydrofuran, arereacted with amines (F), with addition of at least one coupling reagent,preferably selected from the group consisting of carbonyl diimidazole(CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent),N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate(TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate(BOP), optionally in the presence of at least one inorganic base,preferably selected from the group consisting of potassium carbonate andcesium carbonate, or an organic base, preferably selected from the groupconsisting of triethylamine, diisopropylethylamine and pyridine, andoptionally with addition of 4-(dimethylamino)-pyridine or1-hydroxybenzotriazole, to form compounds of formula (G).

Pharmacological Methods

1. Functional Investigation on the Bradykinin 1 Receptor (B1R)

The agonistic or antagonistic action of substances can be determined onthe bradykinin 1 receptor (B1R) of the human and rat species with thefollowing assay. According to this assay, the Ca²⁺ inflow through thechannel is quantified with the aid of a Ca²⁺-sensitive dye (Fluo-4 type,Molecular Probes Europe BV, Leiden, Netherlands) in a fluorescentimaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).

2. Method:

Chinese hamster ovary cells (CHO K1 cells) which are stably transfectedwith the human B1R gene (hB1R cells) or the B1R gene of the rat (rB1Rcells) are used. For functional investigations these cells areplated-out onto black 96-well plates with a clear base (BD Biosciences,Heidelberg, Germany or Greiner, Frickenhausen, Germany) in a density of20,000-35,000 cells/well. Overnight the cells are incubated at 37° C.and 5% CO₂ in culture medium (hB1R cells: Ham's Nutrient Mixture F12,Gibco Invitrogen GmbH, Karlsruhe, Germany or DMEM, Sigma-Aldrich,Taufkirchen, Germany; rB1R cells: D-MEM/F12, Gibco Invitrogen,Karlsruhe, Germany) with 10 vol. % FBS (foetal bovine serum, GibcoInvitrogen GmbH, Karlsruhe, Germany or PAN Biotech GmbH, Aidenbach,Germany).

On the following day the cells are loaded with 2.13 μM Fluo-4 (MolecularProbes Europe BV, Leiden, Netherlands) in HBSS buffer (Hank's bufferedsaline solution, Gibco Invitrogen GmbH, Karlsruhe, Germany) with 2.5 mMprobenecid (Sigma-Aldrich, Taufkirchen, Germany) and 10 mM HEPES(Sigma-Aldrich, Taufkirchen, Germany) for 60 min at 37° C. The platesare subsequently washed twice with HBSS buffer, and HBSS buffer whichadditionally contains 0.1% BSA (bovine serum albumin; Sigma-Aldrich,Taufkirchen, Germany), 5.6 mM glucose and 0.05% gelatine (Merck KGaA,Darmstadt, Germany) is added. After a further incubation of 20 minutesat room temperature, the plates are inserted into the FLIPR for Ca²⁺measurement.

Alternatively they are washed with buffer A (15 mM HEPES, 80 mM NaCl, 5mM KCl, 1.2 mM CaCl₂, 0.7 mM MgSO₄, 2 g/l glucose, 2.5 mM probenecid)and loaded with buffer A with added 2.5 μM Fluo-4 and 0.025% PluronicF127 (Sigma-Aldrich, Taufkirchen, Germany). The cells are then washedtwice with buffer A and incubated for 30 minutes with buffer A, whichadditionally contains 0.05% BSA and 0.05% gelatine, at room temperatureand then used for Ca²⁺ measurement in the FLIPR. The Ca²⁺-dependentfluorescence is measured here before and after addition of substances(λ_(ex)=488 nm, λ_(em)=540 nm). The quantification is performed bymeasuring the highest fluorescence intensity (FC, fluorescence counts)over time.

3. FLIPR Assay:

The FLIPR protocol comprises two additions of substance. Test substances(10 μM) are first pipetted onto the cells and the Ca²⁺ inflow iscompared with the control (hB1R: Lys-Des-Arg⁹ bradykinin>=50 nM; rB1R:Des-Arg⁹ bradykinin 10 μM). The value in % activation based on the Ca²⁺signal after addition of Lys-Des-Arg⁹ bradykinin (>=50 nM) or Des-Arg⁹bradykinin (10 μM) is obtained therefrom. After incubation for 10-20minutes, Lys-Des-Arg⁹ bradykinin (hB1R) or Des-Arg⁹ bradykinin (rB1R) isapplied in the EC₈₀ concentration and the inflow of Ca²⁺ is likewisedetermined.

Antagonists lead to a suppression of the Ca²⁺ inflow. The % inhibitionin comparison with the maximum achievable inhibition is calculated.

The substances are added in varying concentrations in order to determinethe IC₅₀ value. Double or triple determinations (n=2 or n=3) areperformed and these are repeated in at least one further independentexperiment (N>=2).

The compounds preferably exhibit a B1R antagonistic action on the humanreceptor and/or on the rat receptor.

The invention is described below with reference to examples, withoutlimiting the general concept or scope of the invention.

EXAMPLES List of Abbreviations

DIPEA diisopropylethylamine

EDCI N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride

h hour(s)

HOBt 1-hydroxy-1H-benzotriazole

conc. concentrated

min minute(s)

N normal

RT room temperature

THF tetrahydrofuran

TFA trifluoroacetic acid

abs. absolute

eq. equivalent(s)

equiv. equivalent(s)

Boc tert-butyl carbamate

DCM dichloromethane

M molar

EtOAc ethyl acetate

Et₃N triethylamine

Cbz benzyl carbamate

DMF dimethyl formamide

DBU 1,8-diazabicyclo[5.4.0]undec-7-ene

1) Synthesis of Amino Indole Esters A Structural unit A-01: tert-Butyl2-(7-amino-1H-indol-1-yl) acetate Stage 1: tert-Butyl2-(7-nitro-1H-indol-1-yl) acetate

7-Nitroindole (77 mmol, 1 equiv.) dissolved in dimethyl formamide (25ml) was added slowly to a suspension of sodium hydride (85 mmol, 1.1equiv.) in dimethyl formamide (75 ml) at 0° C., the reaction mixtureobtained was stirred for 30 min, then tert-butyl bromoacetate (85 mmol,1.1 equiv.) was added and the mixture was stirred for 12 h at roomtemperature.

The reaction mixture was processed by adding methanol, diluting withdiethyl ether and washing 3 times with water. The organic phase wasdried over magnesium sulfate and concentrated under reduced pressure.The solid that accumulated was filtered out and washed with a littlediethyl ether. The desired product was obtained in this way in a yieldof 89% (75 mmol).

Stage 2: tert-Butyl 2-(7-amino-1H-indol-1-yl) acetate (A-01)

10% palladium on activated carbon (500 mg) was added to a solution oftert-butyl 2-(7-nitro-1H-indol-1-yl)acetate (68 mmol, 1 equiv.) in ethylacetate/methanol (1:1) and the mixture obtained was hydrogenated under2.5 bar hydrogen pressure for 12 h. The reaction mixture was processedby filtering over celite, rewashing with ethyl acetate, concentratingunder reduced pressure and recrystallizing from isopropanol. The desiredproduct was obtained in a yield of 80% (54.4 mmol).

Structural unit A-02: tert-Butyl 2-(6-amino-1H-indol-1-yl) acetate Stage1: tert-Butyl 2-(6-nitro-1H-indol-1-yl) acetate

6-Nitroindole (77 mmol, 1 equiv.) dissolved in dimethyl formamide (25ml) was added slowly to a suspension of sodium hydride (85 mmol, 1.1equiv.) in dimethyl formamide (70 ml) at 0° C., the reaction mixtureobtained was stirred for 30 min, then tert-butyl bromoacetate (85 mmol,1.1 equiv.) was added and the mixture was stirred for 12 h at roomtemperature.

The reaction mixture was processed by adding methanol, diluting withdiethyl ether and washing 3 times with water. The organic phase wasdried over magnesium sulfate and concentrated under reduced pressure andrecrystallized from diethyl ether. The desired product was obtained inthis way in a yield of 69% (53 mmol).

Stage 2: tert-Butyl 2-(6-amino-1H-indol-1-yl) acetate (A-02)

10% palladium on activated carbon (500 mg) was added to a solution oftert-butyl 2-(6-nitro-1H-indol-1-yl)acetate (54 mmol, 1 equiv.) in ethylacetate/methanol (3:1) and the mixture obtained was hydrogenated under2.5 bar hydrogen pressure for 12 h. The reaction mixture was processedby filtering over celite, rewashing with ethyl acetate and concentratingunder reduced pressure. The desired product was obtained in aquantitative yield.

Structural unit A-03: Methyl 3-(6-amino-1H-indol-1-yl) propanoate Stage1: Methyl 3-(6-nitro-1H-indol-1-yl) propanoate

1,8-Diazabicyclo[5.4.0]undec-7-ene (23 mmol, 0.5 equiv.) was added to asolution of 6-nitroindole (46 mmol, 1 equiv.) and methyl acrylate (69mmol, 1.5 equiv.) in acetonitrile (25 ml) at 0° C. and stirred for 12 hat room temperature. The reaction solution was concentrated underreduced pressure and the residue was purified by column chromatography(silica, ethyl acetate/hexane). The desired product was obtained in ayield of 80% (36.8 mmol).

Stage 2: Methyl 3-(6-amino-1H-indol-1-yl) propanoate (A-03)

10% palladium on activated carbon (500 mg) was added to a solution ofmethyl 3-(6-nitro-1H-indol-1-yl) propanoate (60 mmol, 1 equiv.) in ethylacetate/methanol (3:1) and the mixture obtained was hydrogenated under2.5 bar hydrogen pressure for 12 h. The reaction mixture was processedby filtering over celite, rewashing with ethyl acetate and concentratingunder reduced pressure. The desired product was obtained in aquantitative yield.

Structural unit A-04: Methyl 3-(7-amino-1H-indol-1-yl) propanoate Stage1: Methyl 3-(7-nitro-1H-indol-1-yl) propanoate

1,8-Diazabicyclo[5.4.0]undec-7-ene (31 mmol, 0.5 equiv.) was added to asolution of 7-nitroindole (62 mmol, 1 equiv.) and methyl acrylate (93mmol, 1.5 equiv.) in acetonitrile (30 ml) at 0° C. and stirred for 12 hat room temperature. The reaction solution was concentrated underreduced pressure and the residue was purified by column chromatography(silica, ethyl acetate/hexane). The desired product was obtained in ayield of 38% (23 mmol).

Stage 2: Methyl 3-(7-amino-1H-indol-1-yl) propanoate (A-04)

10% palladium on activated carbon (500 mg) was added to a solution ofmethyl 3-(7-nitro-1H-indol-1-yl) propanoate (43 mmol, 1 equiv.) in ethylacetate/methanol (3:1) and the mixture obtained was hydrogenated under2.5 bar hydrogen pressure for 12 h. The reaction mixture was processedby filtering over celite, washing with ethyl acetate and concentratingunder reduced pressure. The desired product was obtained in aquantitative yield.

2) Synthesis of Sulfonyl Chlorides C Sulfonyl chloride C-01:2-(Trifluoromethyl)phenyl-1-sulfonyl chloride

(CAS No: 776-04-5) is commercially available from e.g. ABCR.

Sulfonyl chloride C-02: 4-Chloro-2,5-dimethylphenyl-1-sulfonyl chloride

(CAS No: 88-49-3) is commercially available from e.g. ABCR.

Sulfonyl chloride C-03: 4-Methoxy-2,6-dimethylphenyl-1-sulfonyl chloride

Chlorosulfuric acid (1.83 ml, 2.3 equiv.) in dichloromethane (10 ml) wasadded dropwise to a solution of 3,5-dimethyl anisole (1.632 g, 11.982mmol) in dichloromethane (15 ml) over 20 min at 0° C. The reactionmixture was then stirred for 10 min at room temperature. The reactionmixture was poured over iced water (3 ml, 5 equiv. relative tochlorosulfuric acid) and the aqueous phase was extracted withdichloromethane (3×100 ml). The organic phase was dried (Na₂SO₄) andconcentrated to small volume under vacuum. Yield: 2.6 g (92%)

Sulfonyl chloride C-04: Naphthalene-1-sulfonyl chloride

(CAS No: 85-46-1) is commercially available from e.g. ABCR.

3) Synthesis of Sulfonylated Indole Esters D

General Method for the Synthesis of Sulfonylated Indole Esters D

General procedure GP I—sulfonylation: A solution of sulfonyl chloride C(1.1 equiv.) in dichloromethane was added to a solution of thecorresponding aminoindole ester A (1 equiv.) and diisopropyl ethylamine(1.25 equiv.) in dichloromethane at 0° C. The reaction mixture wasstirred for 12 h at room temperature, then washed 3 times with asaturated sodium hydrogen carbonate solution, dried over magnesiumsulfate and concentrated under reduced pressure. The desired product wasobtained after purification by column chromatography (silica; ethylacetate/hexane).

TABLE 1 Synthesis of sulfonylated indole esters D Ester no. StructureName Amino acid ester (A) D-02

tert-Butyl 2-(7-(4- methoxy-2,6- dimethylphenylsulfon-amido)-1H-indol-1-yl) acetic acid (D-02) tert-Butyl 2-(7-amino-1H-indol-1-yl) acetic acid (A-01) D-03

tert-Butyl 2-(6-(4- methoxy-2,6- dimethylphenylsulfon-amido)-1H-indol-1-yl) acetic acid (D-03) tert-Butyl 2-(6-amino-1H-indol-1-yl) acetic acid (A-02) D-04

tert-Butyl 2-(6-(4-chloro- 2,5- dimethylphenylsulfon-amido)-1H-indol-1-yl) acetic acid (D-04) tert-Butyl 2-(6-amino-1H-indol-1-yl) acetic acid (A-02) D-05

Methyl 3-(6-(4-methoxy- 2,6- dimethylphenylsulfon- amido)-1H-indol-1-yl)propionic acid (D-05) Methyl 3-(6-amino-1H- indol-1-yl) propionic acid(A-03) D-06

tert-Butyl 2-(6-(2- (trifluoromethyl)phenyl- sulfonamido)-1H-indol-1-yl) acetic acid (D-06) tert-Butyl 2-(6-amino-2- 1H-indol-1-yl) aceticacid (A-02) D-07

tert-Butyl 2-(7- (naphthalene-1- sulfonamido)-1H-indol-1- yl) aceticacid (D-07) tert-Butyl 2-(7-amino- 1H-indol-1-yl) acetic acid (A-01)D-08

tert-Butyl 2-(7-(4-chloro- 2,5- dimethylphenylsulfon-amido)-1H-indol-1-yl) acetic acid (D-08) tert-Butyl 2-(7-amino-1H-indol-1-yl) acetic acid (A-01) D-09

Methyl 3-(7-(2- (trifluoromethyl)phenyl- sulfonamido)-1H-indol-1- yl)propionic acid (D-09) Methyl 3-(7-amino-1H- indol-1-yl) propionic acid(A-04) D-10

Methyl 3-(7-(4-chloro- 2,5- dimethylphenylsulfon- amido)-1H-indol-1-yl)propionic acid (D-10) Methyl 3-(7-amino-1H- indol-1-yl) propionic acid(A-04) D-11

Methyl 3-(6-(2- (trifluoromethyl)phenyl- sulfonamido)-1H-indol-1- yl)propionic acid (D-11) Methyl 3-(6-amino-1H- indol-1-yl) propionic acid(A-03) D-12

Methyl 3-(6-(4-chloro- 2,5- dimethylphenylsulfon- amido)-1H-indol-1-yl)propionic acid (D-12) Methyl 3-(6-amino-1H- indol-1-yl) propionic acid(A-03) D-13

tert-Butyl 2-(7-(2- (trifluoromethyl)phenyl- sulfonamido)-1H-indol-1-yl) acetic acid (D-13) tert-Butyl 2-(7-amino- 1H-indol-1-yl) acetic acid(A-01) D-14

Methyl 3-(7-(4-methoxy- 2,6- dimethylphenylsulfon- amido)-1H-indol-1-yl)propionic acid (D-14) Methyl 3-(7-amino-1H- indol-1-yl) propionic acid(A-04) D-15

Methyl 3-(6-(7-chloro-1- oxoisoindolin-2-yl)-1H- indol-1-yl) propionicacid (D-15) D-16

tert-Butyl 2-(6-(7-chloro- 1-oxoisoindolin-2-yl)-1H- indol-1-yl) aceticacid (D-16) D-17

Methyl 3-(7-(7-chloro-1- oxoisoindolin-2-yl)-1H- indol-1-yl) propionicacid (D-17) D-18

tert-Butyl 2-(6- (naphthalene-1- sulfonamido)-1H-indol-1- yl) aceticacid (D-18) tert-Butyl 2-(6-amino- 1H-indol-1-yl) acetic acid (A-02)D-19

Methyl 2-(7-(7-chloro-1- oxoisoindolin-2-yl)-1H- indol-1-yl) acetic acid(D-19) Ester Carboxylic acid chloride (B) Synthesis no. or sulfonylchloride (C) by Yield Note D-02 4-Methoxy-2,6-dimethylphenyl- GP I 62%1-sulfonyl chloride (C-03) (12.0 mmol) D-034-Methoxy-2,6-dimethylphenyl- GP I 53% 1-sulfonyl chloride (C-03) (10.3mmol) D-04 4-Chloro-2,5-dimethylphenyl-1- GP I 62% sulfonyl chloride(C-02) (17.7 mmol) D-05 4-Methoxy-2,6-dimethylphenyl- GP I 69%1-sulfonyl chloride (C-03) (17.4 mmol) D-06 2-(Trifluoromethyl)phenyl-1-GP I 92% sulfonyl chloride (C-01) (16.9 mmol) D-07Naphthalene-1-sulfonyl chloride GP I 43% (a1) (C-04) (7.8 mmol) D-084-Chloro-2,5-dimethylphenyl-1- GP I 52% sulfonyl chloride (C-02) (14.7mmol) D-09 2-(Trifluoromethyl)phenyl-1- GP I 48% sulfonyl chloride(C-01) (10.1 mmol) D-10 4-Chloro-2,5-dimethylphenyl-1- GP I 49% sulfonylchloride (C-02) (9.5 mmol) D-11 2-(Trifluoromethyl)phenyl-1- GP I 60%sulfonyl chloride (C-01) (13.7 mmol) D-12 4-Chloro-2,5-dimethylphenyl-1-GP I 84% sulfonyl chloride (C-02) (21.3 mmol) D-132-(Trifluoromethyl)phenyl-1- GP I 42% sulfonyl chloride (C-01) (8.5mmol) D-14 4-Methoxy-2,6-dimethylphenyl- GP I 17% 1-sulfonyl chloride(C-03) (4.3 mmol) D-15 See E-15 D-16 See E-16 D-17 See E-17 D-18Naphthalene-1-sulfonyl chloride GP I 71% (C-04) (13.0 mmol) D-19 SeeE-19 (a1) The crude product was taken up in 70 ml dichloromethane. Asolid was precipitated which was siphoned off and washed with a littledichloromethane. The parent liquor was concentrated and purified bycolumn chromatography.

4) Synthesis of Sulfonylated Indole Acids E

General Method for the Synthesis of Sulfonylated Indole Acids E

General procedure GP III: Potassium hydroxide (5 to 9 equiv.) and waterwere added to a solution of ester D (1 equiv.) inmethanol/tetrahydrofuran with ice cooling. The mixture was stirred atroom temperature for 5 hours, diluted with water, washed 3 times withdiethyl ether and adjusted to ˜pH 4 with 6N hydrochloric acid. The solidthat was precipitated was filtered out, washed with a little water anddried.

TABLE 2 Synthesis of sulfonylated indole acids E Amino acid no.Structure Name E-02

2-[7-[[(4-Methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-02) E-03

2-[6-[[(4-Methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-03) E-04

2-[6-[[(4-Chloro-2,5-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-04) E-05

3-[6-[[(4-Methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-05) E-06

2-[6-[[[2-(Trifluoromethyl)- phenyl]sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-06) E-07

2-[7-[(Naphthalen-1- ylsulfonyl)amino]-1H-indol-1-yl] acetic acid (E-07)E-08

2-[7-[[(4-Chloro-2,5-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-08) E-09

3-[7-[[[2-(Trifluoromethyl)- phenyl]sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-09) E-10

3-[7-[[(4-Chloro-2,5-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-10) E-11

3-[6-[[[2-(Trifluoromethyl)- phenyl]sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-11) E-12

3-[6-[[(4-Chloro-2,5-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-12) E-13

2-[7-[[[2-(Trifluoromethyl)- phenyl]sulfonyl]amino]-1H-indol-1-yl]acetic acid (E-13) E-14

3-[7-[[(4-Methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1H-indol-1-yl]propionic acid (E-14) E-15

3-[6-(4-Chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-1H-indol-1-yl]propionic acid (E-15) E-16

2-[6-(4-Chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-1H-indol-1-yl] aceticacid (E-16) E-17

3-[7-(4-Chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-1H-indol-1-yl]propionic acid (E-17) E-18

2-[6-[(Naphthalen-1- ylsulfonyl)amino]-1H-indol-1-yl] acetic acid (E-18)E-19

2-[7-(4-Chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-1H-indol-1-yl] aceticacid (E-19) E-20

2-(6-(8-Chloro-4-methyl-1- oxopyrrolo[3,4-b]indol-2(1H,3H,4H)-yl)-1H-indol-1-yl)acetic acid (E-20) E-21

2-(6-(7-Methyl-1-oxoisoindolin-2-yl)- 1H-indol-1-yl)acetic acid (E-21)E-22

2-(6-(5-Methyl-3-oxo-1H-pyrrolo- [1,2-c]imidazol-2(3H)-yl)-1H-indol-1-yl)acetic acid (E-22) E-23

2-(6-(10-Chloro-1-oxo-3,4- dihydropyrazino[1,2-a]indol-2(1H)-yl)-1H-indol-1-yl)acetic acid (E-23) E-24

2-(6-(8-Chloro-1-oxo-3,4- dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)acetic acid (E-24) Amino acid Synthesis no. Amino acidester (D) by Yield Note E-02 tert-Butyl 2-(7-(4-methoxy-2,6- GP III 95%dimethylphenylsulfonamido)-1H- (11.3 mmol) acetic acid (D-02) E-03tert-Butyl 2-(6-(4-methoxy-2,6- GP III 96%dimethylphenylsulfonamido)-1H- (9.9 mmol) indol-1-yl) acetic acid (D-03)E-04 tert-Butyl 2-(6-(4-chloro-2,5- GP III 98%dimethylphenylsulfonamido)-1H- (17.4 mmol) indol-1-yl) acetic acid(D-04) E-05 Methyl 3-(6-(4-methoxy-2,6- GP III 96%dimethylphenylsulfonamido)-1H- (16.3 mmol) indol-1-yl) propionic acid(D-05) E-06 tert-Butyl 2-(6-(2- GP III 107% (a2)(trifluoromethyl)phenylsulfonamido)- (18.0 mmol) 1H-indol-1-yl) aceticacid (D-06) E-07 tert-Butyl 2-(7-(naphthalene-1- GP III 110% (a2)sulfonamido)-1H-indol-1-yl) acetic (8.3 mmol) acid (D-07) E-08tert-Butyl 2-(7-(4-chloro-2,5- GP III 104%dimethylphenylsulfonamido)-1H- (15.3 mmol) indol-1-yl) acetic acid(D-08) E-09 Methyl 3-(7-(2- GP III 97%(trifluoromethyl)phenylsulfonamido)- (9.3 mmol) 1H-indol-1-yl) propionicacid (D-09) E-10 Methyl 3-(7-(4-chloro-2,5- GP III 101%dimethylphenylsulfonamido)-1H- (9.0 mmol) indol-1-yl) propionic acid(D-10) E-11 Methyl 3-(6-(2- GP III 105% (a2)(trifluoromethyl)phenylsulfonamido)- (14.3 mmol) 1H-indol-1-yl)propionic acid (D-11) E-12 Methyl 3-(6-(4-chloro-2,5- GP III 96% (a2)dimethylphenylsulfonamido)-1H- (20.4 mmol) indol-1-yl) propionic acid(D-12) E-13 tert-Butyl 2-(7-(2- GP III 96% (a2)(trifluoromethyl)phenylsulfonamido)- (8.1 mmol) 1H-indol-1-yl) aceticacid (D-13) E-14 Methyl 3-(7-(4-methoxy-2,6- GP III 88%dimethylphenylsulfonamido)-1H- (5.0 mmol) indol-1-yl) propionic acid(D-14) E-15 See E-15 E-16 See E-16 E-17 See E-17 E-18 tert-Butyl2-(6-(naphthalene-1- GP III 92% sulfonamido)-1H-indol-1-yl) acetic (11.8mmol) acid (D-18) E-19 See E-19 E-20 See E-20 E-21 See E-21 E-22 SeeE-22 E-23 See E-23 E-24 See E-24 (a2) After adjusting to pH 4 a brownoil was precipitated which was extracted 3 times with ethyl acetate. Theorganic phases were combined, dried over magnesium sulfate andconcentrated under reduced pressure.

Structural unit E-15:3-(6-(7-Chloro-1-oxoisoindolin-2-yl)-1H-indol-1-yl) propionic acid

Stage 1: A solution of 6-nitroindole (3 mmol) in dry benzene (15 ml) wasadded slowly to a solution of potassium tert-butanolate (1 eq.) in drybenzene (5 ml) in an ice bath under a nitrogen atmosphere. Then methylacrylate (2 eq.) was added and the batch was refluxed for 16 h. Aftercooling to room temperature the reaction mixture was diluted with waterand adjusted to pH 4 with concentrated HCl. The reaction mixture wasextracted with dichloromethane. The organic phase was washedsuccessively with water and saturated NaCl solution, dried overanhydrous sodium sulfate and concentrated to small volume under reducedpressure. The crude product was purified by column chromatography withsilica gel (DCM/MeOH) and the desired first-stage product was obtained.Yield: 53%

Stage 2: A mixture of the first-stage product (0.9 mmol), iron powder(3.3 eq.) and concentrated HCl (0.1 ml) was refluxed in ethanol (5 ml)for 4 h. After cooling to RT it was filtered through celite. Thefiltrate was concentrated to small volume, the concentrated mass wastaken up with water and adjusted to pH 4 with concentrated HCl. Themixture was extracted with dichloromethane. The organic phase was washedsuccessively with water and saturated NaCl solution, dried overanhydrous sodium sulfate and concentrated to small volume under reducedpressure. The crude product obtained was used directly in the nextstage. Yield: 90%

Stage 3: A mixture of the second-stage product (0.45 mmol),2-bromomethyl-6-chlorobenzoate (1 eq.) and TEA (1.2 eq.) was refluxed inbenzene (10 ml) under a nitrogen atmosphere for 16 h. The reactionmixture was concentrated to small volume and the concentrated mass wastaken up with DCM. The organic phase was washed successively with waterand saturated NaCl solution, dried over anhydrous sodium sulfate andconcentrated to small volume under reduced pressure. The crude productwas purified by column chromatography with silica gel (DCM/MeOH) and thedesired third-stage product was obtained. Yield: 48.5%

Stage 4: LiOH.H₂O (5 eq.) was added to a suspension of the third-stageproduct (0.5 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) andwater (30 ml) and the reaction mixture was stirred overnight at 25° C.Methanol and THF were drawn off completely. The aqueous phase wasacidified with 1(N)HCl and then filtered. The white solid was stirredfor 1 h in a mixture of 350 ml acetone and 50 ml methanol. Afterfiltration the white solid was dried under reduced pressure and thedesired pure product E-15 was obtained. Yield: 61%

Structural unit E-16:2-(6-(7-Chloro-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetic acid

Stage 1: 6-Nitroindole (3 mmol) dissolved in DMF (5 ml) was added to asuspension of sodium hydride (1.5 eq.) in DMF (5 ml) at 0° C. andstirred for 30 min. Then tert-butyl-bromoacetate (1.2 eq.) was added andthe mixture was stirred at RT for 15 h. The batch was quenched withsaturated NH₄Cl solution and extracted with ethyl acetate. The organicphase was washed successively with water and saturated NaCl solution,dried over anhydrous sodium sulfate and concentrated to small volumeunder reduced pressure. The crude product was purified by columnchromatography with silica gel (ethyl acetate/hexane) and the desiredfirst-stage product was obtained. Yield: 47%

Stage 2: A mixture of the first-stage product (1.44 mmol), iron powder(4 eq.) and ammonium chloride (0.4 eq.) was refluxed in ethanol (10 ml)for 4 h. After cooling to RT it was filtered through celite. Thefiltrate was concentrated to small volume and the concentrated mass wastaken up with water. It was extracted with dichloromethane. The organicphase was washed successively with water and saturated NaCl solution,dried over anhydrous sodium sulfate and concentrated to small volumeunder reduced pressure. The crude product was purified byrecrystallization with ethyl acetate/hexane. Yield: 61%

Stage 3: A mixture of the second-stage product (25 mmol),2-bromomethyl-6-chlorobenzoate (1.2 eq.) and TEA (1.2 eq.) was refluxedin benzene (150 ml) under a nitrogen atmosphere for 16 h. The reactionmixture was concentrated to small volume and the concentrated mass wastaken up with DCM. The organic phase was washed successively with waterand saturated NaCl solution, dried over anhydrous sodium sulfate andconcentrated to small volume under reduced pressure. The crude productwas purified by column chromatography with silica gel (DCM/MeOH) and thedesired third-stage product was obtained. Yield: 42%

Stage 4: LiOH.H₂O (5 eq.) was added to a suspension of the third-stageproduct (15 mmol) in methanol (25 ml), tetrahydrofuran (25 ml) and water(50 ml) and the reaction mixture was stirred overnight at 25° C.Methanol and THF were drawn off completely. The aqueous phase wasacidified with 1(N)HCl and then filtered. The white solid was driedunder reduced pressure and the desired product E-16 was obtained. Yield:98%

Structural unit E-17:3-(7-(7-Chloro-1-oxoisoindolin-2-yl)-1H-indol-1-yl) propionic acid

Stage 1: The DBU was added slowly to a solution of 7-nitroindole (6mmol) in acetonitrile (10 ml) at 0° C. The solution was stirred for 20 hat RT. Then the reaction mixture was concentrated and the crude mass wasdiluted with ethyl acetate. The ethyl acetate phase was washed withsaturated NH₄Cl solution, water and saturated NaCl solution, dried overanhydrous sodium sulfate and concentrated to small volume under reducedpressure. The crude product was purified by column chromatography withsilica gel (ethyl acetate/hexane) and the desired first-stage productwas obtained. Yield: 35%

Stage 2: Pd/C 10% was added to a solution of the first-stage product(1.2 mmol) in methanol (10 ml) under a nitrogen atmosphere and themixture was hydrogenated for 16 h under a pressure of 2 bar. The batchwas filtered and the filtrate concentrated to small volume. Thesecond-stage product was obtained and was used directly in the nextstage with no further purification. Yield: 63.5%

Stage 3: A mixture of the second-stage product (0.45 mmol),2-bromomethyl-6-chlorobenzoate (1 eq.) and TEA (1.2 eq.) was refluxed inbenzene (10 ml) under a nitrogen atmosphere for 16 h. The reactionmixture was concentrated to small volume and the concentrated mass wastaken up with DCM. The organic phase was washed successively with waterand saturated NaCl solution, dried over anhydrous sodium sulfate andconcentrated to small volume under reduced pressure. The crude productwas purified by column chromatography with silica gel (DCM/MeOH) and thedesired third-stage product was obtained. Yield: 40%

Stage 4: LiOH.H₂O (5 eq.) was added to a suspension of the third-stageproduct (0.5 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) andwater (30 ml) and the reaction mixture was stirred overnight at 25° C.Methanol and THF were drawn off completely. The aqueous phase wasacidified with 1(N)HCl and then filtered. The white solid was stirredfor 1 h in a mixture of 350 ml acetone and 50 ml methanol. Afterfiltration the white solid was dried under reduced pressure and thedesired pure product E-17 was obtained. Yield: 55%

Structural unit E-19:2-(7-(7-Chloro-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetic acid

Stage 1: 6-Nitroindole (30 mmol) dissolved in DMF (100 ml) was added toa suspension of sodium hydride (1.5 eq.) in DMF (5 ml) at 0° C. andstirred for 30 min. Then tert-butyl-bromoacetate (1.2 eq.) was added andthe mixture was stirred at RT for 15 h. The batch was quenched withsaturated NH₄Cl solution and extracted with ethyl acetate. The organicphase was washed successively with water and saturated NaCl solution,dried over anhydrous sodium sulfate and concentrated to small volumeunder reduced pressure. The crude product was purified by columnchromatography with silica gel (ethyl acetate/hexane) and the desiredfirst-stage product was obtained. Yield: 82%

Stage 2: Pd/C 10% was added to a solution of the first-stage product(1.44 mmol) in methanol (10 ml) under a nitrogen atmosphere and themixture was hydrogenated for 16 h under a pressure of 2 bar. The batchwas filtered and the filtrate concentrated to small volume. Thesecond-stage product was obtained and was used directly in the nextstage with no further purification. Yield: 89%

Stage 3: A mixture of the second-stage product (25 mmol),2-bromomethyl-6-chlorobenzoate (1.2 eq.) and TEA (1.2 eq.) was refluxedin benzene (150 ml) under a nitrogen atmosphere for 16 h. The reactionmixture was concentrated to small volume and the concentrated mass wastaken up with DCM. The organic phase was washed successively with waterand saturated NaCl solution, dried over anhydrous sodium sulfate andconcentrated to small volume under reduced pressure. The crude productwas purified by column chromatography with silica gel (DCM/MeOH) and thedesired third-stage product was obtained. Yield: 48.5%

Stage 4: LiOH.H₂O (5 eq.) was added to a suspension of the third-stageproduct (15 mmol) in methanol (25 ml), tetrahydrofuran (25 ml) and water(50 ml) and the reaction mixture was stirred overnight at 25° C.Methanol and THF were drawn off completely. The aqueous phase wasacidified with 1(N)HCl and then filtered. The white solid was stirredfor 1 h in a mixture of 350 ml acetone and 50 ml methanol. Afterfiltration the white solid was dried under reduced pressure and thedesired pure product E-18 was obtained. Yield: 80%

Structural unit E-20:2-(6-(8-Chloro-4-methyl-1-oxopyrrolo[3,4-b]indol-2(1H,3H,4H)-yl)-1H-indol-1-yl)aceticacid

Stage 1: (E)-Methyl 2-(2-chloro-6-nitrophenyl)-3-hydroxybut-2-enoate

Methyl acetoacetate (59.82 mmol, 2.1 equiv.) was added dropwise at 0° C.to a suspension of NaH (65.52 mmol, 2.3 equiv.) in DMF (40 ml). Then themixture was stirred for 10 min and subsequently heated to 25° C.2-Fluoro-3-chloronitrobenzene (28.49 mmol, 1.0 equiv.) was cooled withan ice bath in a reaction flask, and the NaH suspension was added. Thenstirring was carried out for 16 h at 25° C. 2 M HCl (5 ml) and water (10ml) were then added, and extraction with diethyl ether (3×20 ml) wascarried out. The combined organic phases were washed with water (10 ml)and sat. NaCl solution (20 ml), dried over Na₂SO₄ and reduced underreduced pressure. The residue was purified by column chromatography (5%ethyl acetate in hexane). Yield: 51%

Stage 2: Methyl 4-chloro-2-methyl-1H-indole-3-carboxylate

(E)-Methyl 2-(2-chloro-6-nitrophenyl)-3-hydroxybut-2-enoate (14.76 mmol,1.0 equiv.) was dissolved in acetic acid (96 ml), and a solution ofTiCl₃ (20%-w/w in 2 N HCl, 71.6 ml) was added, with stirring. Themixture was then heated for 5-10 min at 90° C. The reaction mixture wascooled with an ice bath and diluted with water and DCM/methanol (9:1,100 ml). The phases were separated and the organic phase was washed withwater and sat. NaCl solution. Drying over Na₂SO₄ was then carried out,followed by concentration under reduced pressure. The product wascrystallized from hexane. Yield: 91%

Stage 3: Methyl 4-chloro-1,2-dimethyl-1H-indole-3-carboxylate

Methyl 4-chloro-2-methyl-1H-indole-3-carboxylate (13.45 mmol, 1.0equiv.) was dissolved in DMF (7 ml) and added at 0° C. to a suspensionof NaH (26.90 mmol, 2.0 equiv.) in DMF (13 ml). The mixture was thenstirred for 30 min. Methyl iodide (20.17 mmol, 1.5 equiv.) was addeddropwise at 0° C. and stirring was carried out for 2 h at 25° C. Thereaction mixture was diluted with NH₄Cl solution (20 ml) and extractedwith ethyl acetate (3×50 ml). The combined organic phases were washedwith water and sat. NaCl solution (in each case 50 ml), dried overNa₂SO₄ and concentrated to dryness under reduced pressure. Yield: 72%

Stage 4: Methyl2-(bromo-methyl)-4-chloro-1-methyl-1H-indole-3-carboxylate

Methyl 4-chloro-1,2-dimethyl-1H-indole-3-carboxylate (9.70 mmol, 1.0equiv.) was dissolved in CCl₄ (97 ml), and NBS (9.70 mmol, 1.0 equiv.)and benzoyl peroxide (0.19 mmol, 0.02 equiv.) were added. The mixturewas heated for 1 h at 85° C. The resulting succinimide was filtered out,the filtrate was concentrated, and the residue was purified by columnchromatography (20% ethyl acetate in hexane). Yield: 48%

Stage 5: Methyl2-((1-(2-tert-butoxy-2-oxoethyl)-1H-indol-6-ylamino)methyl)-4-chloro-1-methyl-1H-indole-3-carboxylate

Methyl 2-(bromo-methyl)-4-chloro-1-methyl-1H-indole-3-carboxylate (1.10mmol, 1.0 equiv.) and tert-butyl 2-(6-amino-1H-indol-1-yl)acetate(intermediate A) (1.10 mmol, 1.0 equiv.) were dissolved in benzene (5ml) and triethylamine (1.3 mmol, 1.2 equiv.) and refluxed for 16 h. Thereaction mixture was cooled to 25° C., diluted with ethyl acetate andwashed with water and sat. NaCl solution. Drying over Na₂SO₄ was thencarried out, followed by concentration under reduced pressure. The crudeproduct was purified by column chromatography (40% ethyl acetate inhexane). Yield: 55%

Stage 6: tert-Butyl2-(6-(8-chloro-4-methyl-1-oxopyrrolo[3,4-b]indol-2(1H,3H,4H)-yl)-1H-indol-1-yl)acetate

Methyl2-((1-(2-tert-butoxy-2-oxoethyl)-1H-indol-6-ylamino)methyl)-4-chloro-1-methyl-1H-indole-3-carboxylate(2.416 mmol, 1 equiv.) was dissolved in dichloromethane (36 ml), and(CH₃)₃Al (2 M solution in toluene, 4.83 mmol) was added at 0° C., undernitrogen. After 10 min, the reaction mixture was heated to 25° C. andthen stirred for 2 h. The reaction mixture was diluted withdichloromethane and hydrolysed with 2 M HCl. The phases were separated,and the organic phase was washed with water and sat. NaCl solution (ineach case 10 ml). Drying over Na₂SO₄ was then carried out, followed byconcentration under reduced pressure. The product was crystallized fromethyl acetate. Yield: 89%

Stage 7:2-(6-(8-Chloro-4-methyl-1-oxopyrrolo[3,4-b]indol-2(1H,3H,4H)-yl)-1H-indol-1-yl)aceticacid

tert-Butyl2-(6-(8-chloro-4-methyl-1-oxopyrrolo[3,4-b]indol-2(1H,3H,4H)-yl)-1H-indol-1-yl)acetate(1.6 mmol, 1 equiv.) was dissolved in DCM (40 ml); TFA (16 ml) was addedand the mixture was stirred for 2 h at 25° C. The solvent was reducedunder reduced pressure, dichloromethane was added 2× to the residue, andin each case concentration to dryness again was carried out. The residuewas used in the next step without being purified further.

Intermediate A Stage 1: tert-Butyl 2-(6-nitro-1H-indol-1-yl)acetate

NaH (4.5 mmol, 1.5 equiv.) was suspended in DMF (5 ml), and6-nitro-indole (3 mmol, 1 equiv.), dissolved in DMF (5 ml), was added at0° C. The mixture was stirred for 30 min. Then tert-butyl bromoacetate(3.6 mmol, 1.2 equiv.) was added and the mixture was stirred for 15 h at25° C. The reaction mixture was hydrolysed with ammonium chloride andextracted with ethyl acetate (3×20 ml). The combined organic phases werewashed with water and sat. NaCl solution (in each case 20 ml), driedover Na₂SO₄ and concentrated under reduced pressure. The crude productwas purified by column chromatography. Yield: 47%

Stage 2: tert-Butyl 2-(6-amino-1H-indol-1-yl)acetate

A mixture of tert-butyl 2-(6-nitro-1H-indol-1-yl)acetate (1.44 mmol, 1equiv.), iron powder (5.76 mmol, 4 equiv.), ammonium chloride (4 equiv.)and ethanol (10 ml) was stirred for 4 h at boiling temperature. Thereaction mixture was cooled to 25° C. and filtered over celite. Thefiltrate was concentrated, diluted with water (50 ml) and extracted withdichloromethane (3×20 ml). The combined organic phases were washed withwater and sat. NaCl solution (in each case 10 ml), dried over Na₂SO₄ andconcentrated under reduced pressure. For purification, the product wasrecrystallized from ethyl acetate/hexane. Yield: 61%

Structural unit E-21:2-(6-(7-Methyl-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetic acid

Stage 1: Methyl 2,6-dimethylbenzoate

K₂CO₃ (10.1 mmol, 1.5 equiv.) and dimethyl sulfate (7.4 mmol, 1.1equiv.) were added at 25° C. to a solution of 2,6-dimethylbenzoic acid(6.7 mmol, 1 equiv.), and the mixture was stirred for 1 h. The solventwas reduced under reduced pressure, the residue was taken up in ethylacetate (100 ml), and water (20 ml) was added. The phases were separatedand the aqueous phase was extracted with ethyl acetate (2×50 ml). Thecombined organic phases were washed with sat. NaCl solution, dried overNa₂SO₄ and concentrated under reduced pressure. The crude product wasused in the next stage without being purified further. Yield:quantitative

Stage 2: Methyl 2-(bromo-methyl)-6-methylbenzoate

NBS (40.85 mmol, 1 equiv.) and benzoyl peroxide (10.21 mmol, 0.25equiv.) were added to a solution of methyl 2,6-dimethylbenzoate (40mmol, 1 equiv.) in CCL₄ (75 ml), and the mixture was heated for 20 minat boiling temperature. The reaction mixture was filtered out overcelite and the filtrate was concentrated under reduced pressure. Theresidue was purified by column chromatography (1.5% ethylacetate/hexane). Yield: 32%

Stage 3: Ethyl2-(6-(7-methyl-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetate

Ethyl 2-(6-amino-1H-indol-1-yl)acetate (intermediate B) (7.66 mmol, 1equiv.) was dissolved in benzene (30 ml), and methyl2-(bromo-methyl)-6-methylbenzoate (8.42 mol, 1.1 equiv.) and TEA (9.19mmol, 1.2 equiv.) were added at 25° C. and the mixture was refluxed for12 h. The reaction mixture was reduced under reduced pressure and theresidue was taken up in dichloromethane (30 ml), washed with water andsat. NaCl solution (5 ml), dried over sodium sulfate and concentratedunder reduced pressure. The crude product was purified by columnchromatography (10% ethyl acetate in hexane). Yield: 64%

Stage 4: 2-(6-(7-Methyl-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetic acid

NaOH (1.86 mmol, 1.3 equiv.), dissolved in water (6 ml), was added to asolution of ethyl2-(6-(7-methyl-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetate (1.44 mmol, 1equiv.) in THF/MeOH (1:1, 5 ml), and the mixture was stirred for 2 h at25° C. The reaction solution was concentrated under reduced pressure,and the aqueous residue was adjusted to pH 3 with 1 M HCl and extractedwith ethyl acetate (3×50 ml). The combined organic phases were driedover Na₂SO₄ and concentrated under reduced pressure. Yield: quantitative

Intermediate B Stage 1: Ethyl 2-(6-nitro-1H-indol-1-yl)acetate

NaH (37 mmol, 2 equiv.) was taken up in DMF (25 ml) and cooled to 0° C.6-Nitro-1H-indole (18.5 mmol, 1 equiv.) was added in portions, and themixture was stirred for 1 h at 25° C. The reaction mixture was cooled to0° C. again, ethyl bromoacetate (22.22 mmol, 1.2 equiv.) was addeddropwise, and the mixture was stirred for 2 h at 25° C. The reactionmixture was then poured into ice-water and extracted with ethyl acetate(2×100 ml). The combined organic phases were washed with sat. NaClsolution (30 ml), dried over Na₂SO₄ and concentrated under reducedpressure. The product was crystallized from hexane and was used in thenext step without being purified further. Yield: 57%

Stage 2: Ethyl 2-(6-amino-1H-indol-1-yl)acetate

A mixture of ethyl 2-(6-nitro-1H-indol-1-yl)acetate (20.96 mmol, 1equiv.), iron powder (83.8 mmol, 4 equiv.), ammonium chloride (83.87mmol, 1 equiv.) and ethanol/water (2.5:1, 56 ml) was stirred for 2 h atboiling temperature. The reaction mixture was cooled to 25° C. andfiltered over celite. The filtrate was diluted with ethyl acetate andwater, the phases were separated, and the organic phase was washed withsodium hydrogen carbonate solution and sat. NaCl solution, dried overNa₂SO₄ and concentrated under reduced pressure. The crude product waspurified by column chromatography (15% ethyl acetate in hexane). Yield:55%

Structural unit E-22:2-(6-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-1H-indol-1-yl)aceticacid

Stage 1: tert-Butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate

(Boc)₂O (5.498 mmol, 1.2 equiv.) was added at 0° C. to a solution of5-methyl-1H-pyrrole-2-carbaldehyde (4.58 mmol, 1.0 equiv.) and DMAP(0.3665 mmol, 0.08 equiv.) in acetonitrile (10 ml), and the mixture wasstirred for 2 h at 25° C. The solvent was reduced under reduced pressureand the residue was purified by column chromatography (4% ethyl acetatein hexane). Yield: 94%

Stage 2: tert-Butyl2-((1-(2-tert-butoxy-2-oxoethyl)-1H-indol-6-ylamino)methyl)-5-methyl-1H-pyrrole-1-carboxylate

A solution of tert-butyl 2-(6-amino-1H-indol-1-yl)acetate (intermediateA—for synthesis see above) (1.7368 mmol, 1.1 equiv.) in DCM (3 ml) wasadded at 0° C. to tert-butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate(1.5789 mmol, 1.0 equiv.), dissolved in DCM (12 ml), and the mixture wasstirred for 30 min at 25° C. At 0° C., Na(OAc)₃BH (4.7368 mmol, 3.0equiv.) was added in portions, and then the mixture was stirred for 12 hat 25° C. The reaction mixture was diluted with DCM (100 ml), washedwith water and sat. NaCl solution (in each case 2×50 ml), dried overNa₂SO₄ and concentrated under reduced pressure. The crude product waspurified by column chromatography (5% ethyl acetate in hexane). Yield:58%

Stage 3:2-(6-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-1H-indol-1-yl)aceticacid

NaH (2.0 equiv., 60% in mineral oil) was suspended at 0° C. in THF (6ml). A solution of tert-butyl2-((1-(2-tert-butoxy-2-oxoethyl)-1H-indol-6-ylamino)methyl)-5-methyl-1H-pyrrole-1-carboxylate(0.797 mmol, 1.0 equiv.) in THF (2 ml) was added, and the mixture wasstirred for 14 h at 25° C. The reaction mixture was hydrolysed withwater (50 ml) and diluted with ethyl acetate (100 ml). The aqueous phasewas adjusted to an acidic pH value with acetic acid and extracted withethyl acetate (2×50 ml). The combined organic phases were dried overNa₂SO₄ and concentrated under reduced pressure. The product wascrystallized from the residue with hexane. Yield: 81%

Structural unit E-23:2-(6-(10-Chloro-1-oxo-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-1H-indol-1-yl)aceticacid

Stage 1: Ethyl 3-chloro-1H-indole-2-carboxylate

Ethyl 1H-indole-2-carboxylate (26.45 mmol, 1.0 equiv.) was dissolved inCCl₄ (26 ml); NCS (29.10 mmol, 1.1 equiv.) was added and the mixture washeated for 16 h at boiling temperature. The resulting solid was filteredout, and the filtrate was washed with water (2×50 ml) and sat. NaClsolution (50 ml), dried over Na₂SO₄ and concentrated under reducedpressure. The crude product was purified by column chromatography (10%ethyl acetate in hexane). Yield: 73%

Stage 2: 3-Chloro-1H-indole-2-carboxylic acid

Ethyl 3-chloro-1H-indole-2-carboxylate (19.28 mmol, 1.0 equiv.) wasdissolved in THF-MeOH—H₂O (2:1:1; 85 ml); LiOH.H₂O (57.84 mmol, 3.0equiv.) was added at 0° C. and the mixture was stirred for 12 h at 25°C. The solvent was reduced under reduced pressure, and the residue wastaken up in water (50 ml), adjusted to pH 3 with 1 M HCl and extractedwith ethyl acetate (2×100 ml). The combined organic phases were driedover Na₂SO₄ and concentrated under reduced pressure, and then theproduct was crystallized with hexane. Yield: 82%

Stage 3: tert-Butyl2-(6-(3-chloro-1H-indole-2-carboxamido)-1H-indol-1-yl)acetate

DIPEA (2.5 equiv.), EDCI (2.73 mmol, 1.2 equiv.) and HOBt (2.73 mmol,1.2 equiv.) were added at 0° C. to a solution of3-chloro-1H-indole-2-carboxylic acid (2.27 mmol, 1.0 equiv.) in DMF (6ml), and the mixture was stirred for 15 min. tert-Butyl2-(6-amino-1H-indol-1-yl)acetate (intermediate A—for synthesis seeabove) (2.27 mmol, 1.0 equiv.) was dissolved in DMF (1 ml) and added,with stirring, and the reaction mixture was then stirred for 12 h at 25°C. The mixture was diluted with dichloromethane (50 ml), washed withsat. ammonium chloride solution (20 ml), water (20 ml) and sat. NaClsolution (20 ml), dried over Na₂SO₄ and concentrated under reducedpressure. The crude product was purified by column chromatography(10-15% ethyl acetate in hexane). Yield: 55%

Stage 4: tert-Butyl2-(6-(10-chloro-1-oxo-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-1H-indol-1-yl)acetate

tert-Butyl 2-(6-(3-chloro-1H-indole-2-carboxamido)-1H-indol-1-yl)acetate(1.41 mmol, 1.0 equiv.) and TBAB (1.41 mmol, 1.0 equiv.) were dissolvedin 1 N NaOH (12 ml); 1,2-dibromoethane (14.18 mmol, 10.0 equiv.) wasadded, and the mixture was stirred for 12 h at 25° C. The reactionmixture was diluted with water (50 ml) and extracted with ethyl acetate(100 ml). The organic phase was washed with sat. NaCl solution (50 ml),dried over Na₂SO₄ and concentrated under reduced pressure, and thedesired product was obtained by purification by column chromatography.Yield: 78%

Stage 5:2-(6-(10-Chloro-1-oxo-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-1H-indol-1-yl)aceticacid

tert-Butyl2-(6-(10-chloro-1-oxo-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-1H-indol-1-yl)acetate(2.22 mmol, 1.0 equiv.) was dissolved in DCM (15 ml); TFA (3 ml) wasadded, and the mixture was stirred for 2 h at 25° C. The solvent wasconcentrated under reduced pressure, and the residue was taken up in DCM(60 ml), washed with water (25 ml) and sat. NaCl solution (25 ml), driedover Na₂SO₄ and concentrated to dryness under reduced pressure. Yield:91%

Structural unit E-24:2-(6-(8-Chloro-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)aceticacid

Stage 1: 4,4-Dichloro-5-(trichloromethyl)-3,4-dihydro-2H-pyrrole

5-Methyl-3,4-dihydro-2H-pyrrole (60.2 mmol, 1.0 equiv.) was dissolved inCCl₄ (100 ml); at 0° C., N-chlorosuccinimide (8.0 equiv.) was added inportions, and the mixture was heated for 72 h at boiling temperature.The reaction mixture was cooled to 0° C., and the resulting solid wasfiltered out and washed with cooled (0° C.) CCL₄ (2×50 ml). The filtratewas concentrated to dryness under reduced pressure. Yield: 90%

Stage 2: Methyl 3-chloro-1H-pyrrole-2-carboxylate

4,4-Dichloro-5-(trichloromethyl)-3,4-dihydro-2H-pyrrole (47.4 mmol, 1.0equiv.) was added to a solution of sodium methanolate (284.5 mmol, 6.0equiv.) in methanol (126 ml), and the mixture was heated for 1.5 h atboiling temperature. The reaction mixture was cooled to 25° C., thesolvent was concentrated under reduced pressure, the residue was takenup in diethyl ether (470 ml), and the mixture was stirred for 30 min.The resulting solid (sodium chloride) was filtered out, and the filtratewas dried over K₂CO₃ and concentrated under reduced pressure. Theresidue was taken up in DCM (600 ml), extracted with 2 N HCl (2×150 ml),dried over Na₂SO₄ and concentrated under reduced pressure. The crudeproduct was used in the next step without being purified further. Yield:83%

Stage 3: 3-Chloro-1H-pyrrole-2-carboxylic acid

Methyl 3-chloro-1H-pyrrole-2-carboxylate (18.86 mmol, 1.0 equiv.) wasdissolved in MeOH—H₂O (2:1, 120 ml); at 0° C., LiOH.H₂O (75.4 mmol, 4equiv.) was added and the mixture was stirred for 16 h at 25° C. Themethanol was concentrated under reduced pressure, and the aqueousresidue was diluted with water (60 ml) and extracted with ethyl acetate(2×50 ml). The aqueous phase was adjusted to pH 3-4 with 1 M HCl, andthe resulting solid was filtered out. Yield: 90%

Stage 4: tert-Butyl2-(5-(3-chloro-1H-pyrrole-2-carboxamido)-1H-indol-1-yl)acetate

DIPEA (4.0 equiv.), EDCI (1.5 equiv.) and HOBt (1.0 equiv.) were addedat 0° C. to a solution of 3-chloro-1H-pyrrole-2-carboxylic acid (5.24mmol, 1.0 equiv.) in DCM (25 ml). The mixture was stirred for 15 min at25° C. and then cooled to 0° C. again. A solution of tert-butyl2-(6-amino-1H-indol-1-yl)acetate (intermediate A—for synthesis seeabove) (5.24 mmol, 1.0 equiv.) in DCM (10 ml) was added, and thereaction mixture was stirred for 16 h at 25° C. It was then diluted withDCM (200 ml), washed with sat. ammonium chloride solution (2×50 ml),sat. sodium hydrogen carbonate solution (2×50 ml) and sat. NaCl solution(2×50 ml), dried over Na₂SO₄ and concentrated under reduced pressure.The crude product was purified by column chromatography (6% methanol inDCM). Yield: 56%

Stage 5: tert-Butyl2-(5-(8-chloro-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)acetate

1,2-Dibromoethane (22.7 mmol, 10.0 equiv.) was added to a solution oftert-butyl2-(5-(8-chloro-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)acetate(2.27 mmol, 1.0 equiv.) and tetrabutylammonium bromide (2.27 mmol, 1.0equiv.) in 1 N NaOH (14 ml), and the mixture was stirred for 12 h at 25°C. The reaction mixture was diluted with water (50 ml) and extractedwith ethyl acetate (150 ml). The organic phase was washed with water(2×50 ml) and sat. NaCl solution (2×50 ml), dried over Na₂SO₄ andconcentrated under reduced pressure. The crude product was purified bycolumn chromatography (10-12% ethyl acetate in hexane). Yield: 93%

Stage 6:2-(5-(8-Chloro-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)aceticacid

A solution of LiOH.H₂O (4.0 equiv.) in water (5 ml) was added at 0° C.to a solution of tert-butyl2-(5-(8-chloro-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1H-indol-1-yl)acetate(1.5 mmol, 1.0 equiv.) in MeOH (20 ml), and the mixture was heated for16 h at 50° C. The methanol was concentrated under reduced pressure, andthe aqueous residue was diluted with water (20 ml) and extracted withethyl acetate (2×15 ml). The aqueous phase was adjusted to pH 4 with 1 MHCl, the desired product precipitating in the form of a white solid. Thesolid was filtered out and dried. Yield: 78%

5) Synthesis of Amine Structural Units F Amine F-01:Dimethyl-(3-piperazin-1-yl propyl)amine

[877-96-3] commercially available from e.g. Acros.

Amine F-02: 1-(1-Methylpiperidin-4-yl)piperazine

[12345-34-56] commercially available from e.g. Aldrich.

Amine F-03: 3-(4-Ethylpiperazin-1-yl) propylamine

[4524-96-3] commercially available from e.g. Fluorochem.

Amine F-05: 4-(2-Pyrrolidin-1-yl ethyl)piperidine

[14759-08-1] commercially available from e.g. ABCR.

Amine F-07: Dimethyl-(4-phenyl piperidin-4-yl)amine dihydrochlorideStage 1:1-Benzyl-4-(dimethylamino)piperidine-4-carbonitrile

208 g (3 eq.) N,N-dimethylamine hydrochloride, 154 g (3 eq.) potassiumcyanide in 154 ml water and 1050 ml (7 eq.) of a 40% dimethylaminesolution were added to a solution of 150 g (1 eq.)1-benzylpiperidin-4-one in 300 ml methanol and the mixture was cooled to0° C. 75 ml (0.5 eq.) concentrated hydrochloric acid were then added at0° C. and the reaction mixture was stirred for 24 h at room temperature.The reaction course was monitored by thin-layer chromatography (20%EtOAc/hexane). Once the conversion was complete, the solid that hadformed was filtered out and washed with iced water (4 l). The solidobtained was then dissolved in ethyl acetate and dried with Na₂SO₄.Following removal of the solvent under reduced pressure, 165 g (85%) ofcrude product were obtained in the form of a solid.

Stage 2: 1-Benzyl-N,N-dimethyl-4-phenylpiperidin-4-amine

A little iodine was added to a mixture of 34.5 g (3.5 eq.) magnesium and100 ml dry diethyl ether, followed over a period of 10 min by 10 g (0.15eq.) bromobenzene, and the mixture was stirred for a further 10 min.Once the reaction had started, 183 g (2.85 eq.) bromobenzene dissolvedin 500 ml diethyl ether were added dropwise over a period of 2 h and themixture was stirred for a further 15 min. 100 g (1 eq.)1-benzyl-4-(dimethylamino)piperidine-4-carbonitrile dissolved in 900 mldiethyl ether were added over a period of 2 h to the Grignard reagentprepared in the preceding step and the mixture was then heated for 12 hat 80° C. The reaction course was monitored by thin-layer chromatography(10% MeOH/CHCl₃). Once the conversion was complete, the reactionsolution was cooled to 0° C., mixed with saturated NH₄Cl solution,extracted with ethyl acetate (3×300 ml) and the combined organic phaseswere dried with Na₂SO₄. Following removal of the solvent under reducedpressure, the residue was purified by column chromatography (silica gel;1% MeOH/CHCl₃). 30 g (35%) of product were obtained in the form of ayellow solid.

Stage 3: Benzyloxycarbonyl-4-(dimethylamino)-4-phenylpiperidine

500 ml (10 eq.) Cbz chloride were added dropwise to 50 g (1 eq.)1-benzyl-N,N-dimethyl-4-phenylpiperidin-4-amine over a period of 1 h andthe reaction mixture obtained was stirred for 2 h at room temperature.The reaction course was monitored by thin-layer chromatography (10%MeOH/CHCl₃). Once the conversion was complete, the reaction mixture wascooled to 0° C., made alkaline with saturated sodium hydrogen carbonatesolution and extracted 3 times with 300 ml EtOAc. The combined organicphases were dried with Na₂SO₄. Following removal of the solvent underreduced pressure, the residue was purified by column chromatography(silica gel; 50% EtOAc/heptane). 12 g (21%) of product were obtained inthe form of an oil.

Stage 4: tert-Butyloxycarbonyl-4-(dimethylamino)-4-phenylpiperidine

12.2 g KOH were added to a solution of 12 g (1 eq.)benzyloxycarbonyl-4-(dimethylamino)-4-phenylpiperidine in 120 ml ethanoland the reaction mixture was refluxed for 48 h. The reaction course wasmonitored by thin-layer chromatography (20% MeOH/CHCl₃). Once theconversion was complete, the solvent was distilled off completely, theresidue suspended in ethyl acetate, filtered, and the organic phasedried over sodium sulfate. Following removal of the solvent underreduced pressure, the crude product was dissolved in dioxane, mixed withsaturated sodium hydrogen carbonate solution and 11.9 g (1.5 eq.) of Bocanhydride and stirred for 30 min at room temperature. Once theconversion was complete, the reaction mixture was extracted with 3×200ml ethyl acetate and the combined organic phases were dried over Na₂SO₄.Following removal of the solvent under reduced pressure, 8.5 g (77%) ofcrude product were obtained in the form of a colorless solid.

Stage 5: N,N-Dimethyl-4-phenylpiperidin-4-amine dihydrochloride

10 equivalents of acetyl chloride were added to a solution oftert-butyloxycarbonyl-4-(dimethylamino)-4-phenylpiperidine in methanolat 0° C. The reaction course was monitored by thin-layer chromatography(10% MeOH/CHCl₃). Once the conversion was complete, the solvent wasremoved under reduced pressure and the product obtained in the form of asolid.

Amine F-08: [1-(2-Aminoethyl)-4-thiophen-2-yl-piperidin-4-yl]dimethylamine trihydrochloride Stage 1:tert-Butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine

500 ml (10 eq.) dimethylamine solution and 109.9 g (5 eq.) dimethylaminehydrochloride were added to a solution of 50 g (1 eq.)tert-butyloxycarbonyl-4-oxopiperidine in 100 ml methanol and the mixturewas cooled to 5° C. 5 ml (0.1 eq.) hydrochloric acid were then addeddropwise to the reaction mixture over a period of 10 min and the mixturewas stirred for 60 min at room temperature. 48.9 g (3 eq.) potassiumcyanide were added in portions to this reaction mixture and the mixturewas stirred for 24 h at room temperature. The reaction course wasmonitored by thin-layer chromatography (50% EtOAc/hexane). Once theconversion was complete, 150 ml water were added to the reaction mixtureand it was extracted 3 times with 100 ml ethyl acetate. The combinedorganic phases were dried with Na₂SO₄. Following removal of the solventunder reduced pressure, crude product was obtained which wasrecrystallized out of hexane. 57 g (90%) of product were obtained in theform of a colorless solid.

Stage 2:tert-Butyloxycarbonyl-4-(dimethylamino)-4-(thiophen-2-yl)piperidine

A little iodine was added to a mixture of 5.6 g (3 eq.) magnesium and 20ml dry diethyl ether, followed over a period of 10 min by 5 g2-bromothiophene, and the mixture was stirred for a further 10 min. Oncethe reaction had started, 33.5 g (2.6 eq.) 2-bromothiophene dissolved in80 ml diethyl ether were added dropwise and the mixture was stirred fora period of 2 h at room temperature. The Grignard reagent prepared inthe preceding step was added dropwise to a solution of 20 g (1 eq.)tert-butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine dissolved in200 ml THF and stirred overnight at room temperature. The reactioncourse was monitored by thin-layer chromatography (50% EtOAc/hexane).Once the conversion was complete, the reaction solution was cooled to 0°C., mixed with saturated NH₄Cl solution, extracted with ethyl acetate(3×100 ml) and the combined organic phases were dried with Na₂SO₄.Following removal of the solvent under reduced pressure, the residue waspurified by column chromatography (alox neutral; 30% EtOAc/hexane). 6.1g (25%) of product were obtained in the form of a white solid.

Stage 3: N,N-Dimethyl-4-(thiophen-2-yl)piperidin-4-amine

HCl gas was passed through a solution of 10 g (1 eq.)tert-butyloxycarbonyl-4-(dimethylamino)-4-(thiophen-2-yl)piperidine inchloroform at 0° C. for ±1 h. Once the conversion was complete, 200 mlwater were added to the reaction mixture, it was adjusted to a pH of ˜8with Na₂CO₃ and then extracted with 15% IPA/CHCl₃. The combined organicphases were dried over Na₂SO₄. Following removal of the solvent underreduced pressure, 6 g (89%) of product were obtained in the form of awhite solid.

Stage 4: tert-Butyl2-(4-(dimethylamino)-4-(thiophen-2-yl)piperidin-1-yl)ethylcarbamate

11.1 g (1.5 eq.) tert-butyl-2-bromoethylcarbamate dissolved in 65 ml THFand 9.19 g (2 eq.) potassium carbonate were added to a solution of 7 g(1 eq.) N,N-dimethyl-4-(thiophen-2-yl)piperidin-4-amine in 40 ml THF.The reaction mixture was heated for 6 h at 70° C. The reaction coursewas monitored by thin-layer chromatography (20% MeOH/CHCl₃). Once theconversion was complete, the solvent was distilled off completely, theresidue mixed with 200 ml water and the aqueous phase extracted with 20%IPA/CHCl₃. The combined organic phases were dried over Na₂SO₄. Followingremoval of the solvent under reduced pressure, the residue was purifiedby column chromatography (silica gel; 10% MeOH/CHCl₃). 9 g (76%) ofproduct were obtained in the form of an oil.

Stage 5:1-(2-Aminoethyl)-N,N-dimethyl-4-(thiophen-2-yl)piperidin-4-amine trishydrochloride

HCl gas was passed through a solution of 9 g (1 eq.) tert-butyl2-(4-(dimethylamino)-4-(thiophen-2-yl)piperidin-1-yl)ethylcarbamate inchloroform at 0° C. for ˜30 min. The reaction mixture was then stirredat room temperature for one hour. The reaction course was monitored bythin-layer chromatography (10% MeOH/CHCl₃). Once the conversion wascomplete, the solvent was removed under reduced pressure and 9 g (97%)of product were obtained in the form of a white solid.

Amine F-09:Dimethyl-[1-(3-methylaminopropyl)-4-thiophen-2-yl-piperidin-4-yl]amineStage 1: tert-Butyl-3-hydroxypropyl(methyl)carbamate

84.2 g (1.2 eq.) sodium carbonate followed by 100 ml water were added inportions to a solution of 50 g (1 eq.) 3-aminopropan-1-ol in 500 ml THFat 0° C. 156.5 ml (1.02 eq.) di-tert-butyl dicarbonate were addeddropwise over a period of 30 min to the solution at 0° C. On completionof the addition, the mixture was stirred for 30 min at room temperature.The reaction course was monitored by thin-layer chromatography (10%MeOH/CHCl₃). Once the conversion was complete, the reaction mixture wasfiltered over celite and the filtrate concentrated under reducedpressure. The residue was mixed with 300 ml water and extracted with2×250 ml ethyl acetate. The combined organic phases were dried overNa₂SO₄. Following removal of the solvent under reduced pressure, 116 g(100%) of product were obtained in the form of an oil.

Stage 2: tert-Butyl-3-(tert-butyldimethylsilyloxy)propylcarbamate

11.6 g (1.3 eq.) imidazole were added to a solution of 23 g (1 eq.)tert-butyl 3-hydroxypropylcarbamate in 230 ml dichloromethane. Thereaction solution was stirred for 10 min at room temperature and thencooled to 0° C. 21.79 g (1.1 eq.) TBDMSCl were added to this solution at0° C. and on completion of the addition the mixture was stirred for 1 hat room temperature. The reaction course was monitored by thin-layerchromatography (30% EtOAc/hexane). Once the conversion was complete, thereaction mixture was filtered over celite and the filtrate mixed with200 ml water and extracted with dichloromethane. The combined organicphases were dried over Na₂SO₄. Following removal of the solvent underreduced pressure, 32 g (84%) of product were obtained in the form of anoil.

Stage 3: tert-Butyl3-(tert-butyldimethylsilyloxy)propyl(methyl)carbamate

50 g (1 eq.) tert-butyl 3-(tert-butyldimethylsilyloxy)propylcarbamatedissolved in 200 ml THF were added dropwise to a mixture of 20.7 g (5eq.) sodium hydride and 300 ml THF at 0° C. After heating the reactionmixture to 10° C., 32.3 ml (3 eq.) methyl iodide were added dropwise. Oncompletion of the addition, the mixture was stirred for 3 h at roomtemperature. The reaction course was monitored by thin-layerchromatography (30% EtOAc/hexane). Once the conversion was complete, thereaction mixture was quenched with saturated NH₄Cl solution and thenextracted with ethyl acetate. The combined organic phases were driedover Na₂SO₄. Following removal of the solvent under reduced pressure, 48g (92%) of product were obtained in the form of an oil.

Stage 4: tert-Butyl-3-hydroxypropyl(methyl)carbamate

482.5 ml (5 eq.) acetic acid dissolved in 386 ml water were addeddropwise over a period of 45 min to a solution of 95.6 g (1 eq.)tert-butyl 3-(tert-butyldimethylsilyloxy)propyl(methyl)carbamatedissolved in 386 ml THF at 0° C. and the reaction mixture was thenstirred for 20 h at room temperature. As the starting product had notyet been completely converted, the mixture was cooled to 0° C., 50 mldilute acetic acid were added over a period of 20 min and the mixturewas stirred for a further 1 h at 0° C. The reaction course was monitoredby thin-layer chromatography (10% EtOAc/hexane). Once the conversion wasalmost complete, the reaction mixture was concentrated under reducedpressure, adjusted to a pH of ˜9 with saturated Na₂CO₃ solution andextracted with 10% IPA/CH₃Cl. The combined organic phases were driedover Na₂SO₄. Following removal of the solvent under reduced pressure,the residue was purified by column chromatography (silica gel; 10%EtOAc/hexane). 40 g (66%) of product were obtained in the form of acolorless oil.

Stage 5: tert-Butyl methyl(3-oxopropyl)carbamate

A catalytic amount of TEMPO was added to a mixture of 20 g (1 eq.)tert-butyl 3-hydroxypropyl(methyl)carbamate in 200 ml dichloromethaneand 17.7 g (2 eq.) sodium hydrogen carbonate in 100 ml water at 0° C.140 ml (7 eq.) NaOCl were then added dropwise over a period of 30 min tothe solution at a temperature of 0° C. and the reaction mixture obtainedwas stirred for a further 15 min at 0° C. The reaction course wasmonitored by thin-layer chromatography (40% EtOAc/hexane). Once theconversion was complete, the reaction mixture was mixed with 150 mlwater and the phases were separated. The organic phase was dried overNa₂SO₄. Following removal of the solvent under reduced pressure, 16 g(85%) of product were obtained in the form of a yellowish oil.

Stage 6: N,N-Dimethyl-4-(thiophen-2-yl)piperidin-4-amine bishydrochloride

HCl gas was passed through a solution of 6 g (1 eq.)tert-butyloxycarbonyl-4-(dimethylamino)-4-(thiophen-2-yl)piperidine in120 ml chloroform at 0° C. for 1 h. The reaction course was monitored bythin-layer chromatography (75% EtOAc/hexane). Once the conversion wascomplete, the solvent was removed under reduced pressure and 5.3 g (98%)of product were obtained in the form of a white solid.

Stage 7: tert-Butyl3-(4-(dimethylamino)-4-(thiophen-2-yl)piperidin-1-yl)propyl(methyl)carbamate

6.4 g (1.3 eq.) tert-butyl methyl(3-oxopropyl)carbamate were added to asolution of 7.5 g (1 eq.)N,N-dimethyl-4-(thiophen-2-yl)piperidin-4-amine bis hydrochloride in 75ml methanol at 0° C. and the reaction mixture was stirred for 15 min at0° C. 4.9 g (3 eq.) sodium cyanoboron hydride were then added inportions and the mixture was stirred for 90 min at room temperature. Thereaction course was monitored by thin-layer chromatography (20%MeOH/CHCl₃). As the conversion was not yet complete, the pH of thereaction mixture was adjusted to 5-6 with acetic acid and the mixturewas stirred for 12 h at room temperature. Once the conversion wascomplete, the methanol was distilled off, water was added, the mixtureobtained was extracted with IPA/chloroform (2×100 ml) and the combinedorganic phases were dried over Na₂SO₄. Following removal of the solventunder reduced pressure, the residue was purified by columnchromatography (silica gel; 5% MeOH/CHCl₃). 8.5 g (84%) of product wereobtained.

Stage 8:N,N-Dimethyl-1-(3-(methylamino)propyl)-4-(thiophen-2-yl)piperidin-4-aminetris hydrochloride

HCl gas was passed through a solution of 1.5 g (1 eq.) tert-butyl3-(4-(dimethylamino)-4-(thiophen-2-yl)piperidin-1-yl)propyl(methyl)carbamatein 30 ml chloroform at 0° C. for ˜30 min. The reaction course wasmonitored by thin-layer chromatography (20% MeOH/CHCl₃). Once theconversion was complete, the solvent was removed under reduced pressure.After trituration with diethyl ether, 1.5 g (98%) of product wereobtained in the form of a white solid. The corresponding free base wasreleased using potassium hydroxide.

Amine F-10: Dimethyl-(4-thiophen-2-yl piperidin-4-yl)aminedihydrochloride Stage 1:tert-Butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine

500 ml (10 eq.) dimethylamine solution and 109.9 g (5 eq.) dimethylaminehydrochloride were added to a solution of 50 g (1 eq.)tert-butyloxycarbonyl-4-oxopiperidine in 100 ml methanol and the mixturewas cooled to 5° C. 5 ml (0.1 eq.) hydrochloric acid were then addeddropwise to the reaction mixture over a period of 10 min and the mixturewas stirred for 60 min at room temperature. 48.9 g (3 eq.) potassiumcyanide were added in portions to this reaction mixture and the mixturewas stirred for 24 h at room temperature. Once the conversion wascomplete, 150 ml water were added to the reaction mixture and it wasextracted 3 times with 100 ml ethyl acetate. The combined organic phaseswere dried with Na₂SO₄. Following removal of the solvent under reducedpressure, crude product was obtained which was recrystallized out ofhexane. 57 g (90%) of product were obtained in the form of a colorlesssolid.

Stage 2:tert-Butyloxycarbonyl-4-(dimethylamino)-4-(thiophen-2-yl)piperidine

A little iodine was added to a mixture of 5.6 g (3 eq.) magnesium and 20ml dry diethyl ether, followed over a period of 10 min by 5 g2-bromothiophene, and the mixture was stirred for a further 10 min. Oncethe reaction had started, 33.5 g (2.6 eq.) 2-bromothiophene dissolved in80 ml diethyl ether were added dropwise and the mixture was stirred fora period of 2 h at room temperature. The Grignard reagent prepared inthe preceding step was added dropwise to a solution of 20 g (1 eq.)tert-butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine dissolved in200 ml THF and stirred overnight at room temperature. Once theconversion was complete, the reaction solution was cooled to 0° C.,mixed with saturated NH₄Cl solution, extracted with ethyl acetate (3×100ml) and the combined organic phases were dried with Na₂SO₄. Followingremoval of the solvent under reduced pressure, the residue was purifiedby column chromatography (alox neutral; 30% EtOAc/hexane). 6.1 g (25%)of product were obtained in the form of a white solid.

Stage 3: N,N-Dimethyl-4-(thiophen-2-yl)piperidin-4-aminebishydrochloride

HCl gas was passed through a solution of 10 g (1 eq.)tert-butyloxycarbonyl-4-(dimethylamino)-4-(thiophen-2-yl)piperidine inchloroform at 0° C. for ±1 h. Once the conversion was complete, 200 mlwater were added to the reaction mixture, it was adjusted to a pH of ˜8with Na₂CO₃ and then extracted with 15% IPA/CHCl₃. The combined organicphases were dried over Na₂SO₄. Following removal of the solvent underreduced pressure, 6 g (89%) of product were obtained in the form of awhite solid.

Amine F-11: Dimethyl-[1-(3-methylaminopropyl)-4-phenylpiperidin-4-yl]amine trihydrochloride Stage 1: tert-Butyl3-(4-(dimethylamino)-4-phenylpiperidin-1-yl)propyl(methyl)carbamate

11.1 g (1.3 eq.) tert-butyl methyl(3-oxopropyl)carbamate were added to asolution of 11 g (1 eq.) N,N-dimethyl-4-phenylpiperidin-4-aminedihydrochloride in 110 ml methanol at 0° C. and the reaction mixture wasstirred for 15 min at 0° C. 6.2 g (3 eq.) sodium cyanoboron hydride werethen added in portions and the mixture was stirred for 30 min at roomtemperature. The reaction mixture obtained was adjusted to a pH of 5-6with acetic acid and stirred for 12 h at room temperature. The reactioncourse was monitored by thin-layer chromatography (20% MeOH/CHCl₃). Asthe conversion was still not complete, 2.4 g sodium cyanoboron hydridewere added and the reaction mixture obtained was adjusted to pH 5-6 withacetic acid and stirred for 60 min at room temperature. Once theconversion was complete, the methanol was distilled off, the mixture wasmade alkaline with saturated NaHCO₃ solution, the mixture obtained wasextracted with chloroform (3×100 ml) and the combined organic phaseswere dried over Na₂SO₄. Following removal of the solvent under reducedpressure, the residue was purified by column chromatography (silica gel;5% MeOH/CHCl₃). 9 g (60%) of product were obtained.

Stage 2:N,N-Dimethyl-1-(3-(methylamino)propyl)-4-phenylpiperidin-4-aminehydrochloride

HCl gas was passed through a solution of 9 g (1 eq.) tert-butyl3-(4-(dimethylamino)-4-phenylpiperidin-1-yl)propyl(methyl)carbamate in100 ml chloroform at 0° C. for 1 h. The reaction course was monitored bythin-layer chromatography (20% MeOH/CHCl₃). Once the conversion wascomplete, the solvent was removed under reduced pressure and aftertrituration with diethyl ether 10 g (100%) of product were obtained inthe form of a white solid.

Amine F-12: [4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]amine hydrochlorideStage 1: 4-(Azetidin-1-yl)-4-phenylcyclohexanone oxime

A solution of 4-(azetidin-1-yl)-4-phenylcyclohexanone (8.4 g) inmethanol (84 ml), water (84 ml) and sodium hydrogen carbonate (10.08 g)was stirred for 5 min at room temperature, then hydroxylaminehydrochloride (6.95 g) was added in portions and the mixture was stirredfor 8 hours at RT. A further 0.4 equiv. of sodium hydrogen carbonate andhydroxylamine hydrochloride were then added, and stirring was carriedout for 16 h at room temperature. Then the reaction mixture wasconcentrated under reduced pressure, the organic phase was separated offand the aqueous phase was extracted with dichloromethane. The combinedorganic phases were dried over sodium sulfate and concentrated underreduced pressure to yield the desired crude product. Yield: 6 g (67%crude)

Stage 2: [4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]-amine

To a solution of the oxime (6 g) obtained above in methanol (60 ml)there was added Raney nickel (2 g) followed by ammonia (30 ml), and thereaction mixture was stirred for 24 hours at room temperature under ahydrogen atmosphere. The reaction mixture was filtered over celite andthen washed with methanol. Methanol was distilled off, and the solidresidue was washed with ethyl acetate/hexane, dried and purified toyield the desired product. Yield: 5 g (88%)

Amine F-13: 2-(1-Pyridin-4-yl-piperidin-4-yl)ethylamine dihydrochloride

(i): tert-Butyl 2-(piperidin-4-yl)ethylcarbamate (0.2 g, 0.876 mmol),4-chloropyridinium chloride (0.197 g, 1.314 mmol) and N-ethyldiisopropylamine (0.37 ml, 2.19 mmol) were refluxed in 2-propanol (10ml) for 15 h. Saturated sodium hydrogen carbonate solution (20 ml) andethyl acetate (50 ml) were added, the phases were separated and theaqueous phase was extracted with ethyl acetate (2×50 ml). The combinedorganic phases were dried over magnesium sulfate and concentrated tosmall volume under vacuum. The crude product was purified by columnchromatography (silica gel) with ethylacetate/dichloromethane/methanol/ammonia (25% eq.) 400/100/50/1. Yield:80 mg, 30%

(ii): Hydrogen chloride (1.25 M solution in methanol, 1.25 ml) was addedto a solution of tert-butyl2-(1-(pyridin-4-yl)piperidin-4-yl)ethylcarbamate (0.12 g, 0.393 mmol) inmethanol (3 ml) at room temperature and the reaction mixture wasrefluxed for 1 h. The solvent was removed under vacuum and the residuewas dried.

Yield: quantitative

Amine F-14: 3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane dihydrochloride

(i): tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (1 g, 3.931mmol), 4-chloropyridinium chloride (1.765 g, 11.794 mmol) andtriethylamine (2.2 ml, 15.725 mmol) were refluxed for 15 h in 1-butanol(50 ml). Saturated sodium hydrogen carbonate solution (30 ml) and ethylacetate (80 ml) were added, the phases were separated and the aqueousphase was extracted with ethyl acetate (2×80 ml). The combined organicphases were dried over magnesium sulfate and concentrated to smallvolume under vacuum. The crude product was purified by columnchromatography (silica gel) with ethyl acetate/hexane/methanol/ammonia(25% eq.) 400/40/40/1. Yield: 0.52 g, 39%

(ii): Hydrogen chloride in methanol (1.25 mol/l, 6.3 ml) was added totert-butyl 9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate(0.52 g, 1.569 mmol) and refluxed for 1 h. The solvent was removed undervacuum, the residue taken up in ethanol (3 ml) and cooled. Acetone (80ml) was added and the mixture was stirred for 30 min in an ice bath. Theprecipitate was separated, washed with diethyl ether and dried undervacuum. Yield: 0.4 g, 83%. Alternatively, the Boc cleavage can also becarried out in the presence of TFA in DCM.

Amine F-15: (1-Pyridin-4-yl-piperidin-4-yl)methylamine dihydrochloride

(i) Potassium carbonate (3 eq.), L-proline (0.4 eq.), CuI (0.2 eq.) and4-bromopyridine (1 eq.) were added to a solution of tert-butylpiperidin-4-ylmethylcarbamate (3 g, 15 mmol) in DMSO under a protectivegas atmosphere. The reaction mixture was heated to 100° C. for 20 hours,diluted with ethyl acetate and saturated sodium chloride solution aftercooling to room temperature, filtered over celite and the residue wasrewashed with ethyl acetate. The phases were separated, dried andconcentrated under reduced pressure. The crude product was processed bycolumn chromatography. Yield 30%

(ii) tert-Butyl (1-(pyridin-4-yl)piperidin-4-yl)methylcarbamate (7 g,24.4 mmol) was dissolved in methanol, cooled in an ice bath, mixed withacetyl chloride (8.6 ml, 121.8 mmol) and stirred at room temperature for3 h. The solvent was removed under reduced pressure and the residue wastaken up in water/dichloromethane. The phases were separated, theaqueous phase was washed with dichloromethane (twice) and freeze dried.Yield: quantitative

Amine F-16: 1-(4-Fluorophenyl)-piperazine

[16141-90-5] commercially available from e.g. Aldrich.

Amine F-17: 2-piperazin-1-yl-pyrimidine

[20980-22-7] commercially available from e.g. Aldrich.

Amine F-18: 1-Pyridin-4-yl piperazine

[1008-91-9] commercially available from e.g. ABCR.

Amine F-19: 4-Pyridin-3-yl piperidin-4-ol

(i) (Apparatus: 1-l three-necked flask with nitrogen balloon flask)Magnesium (5.7 g) was introduced into anhydrous ether (125 ml),1,1-dibromoethane (0.5 g) and isopropylchloride (17.3 ml) were addeddropwise and the mixture was stirred for 15 min to initiate themagnesium. A solution of 3-bromopyridine (25 g) in anhydroustetrahydrofuran (400 ml) was added dropwise over 20 min at 40° C., thenthe mixture was refluxed for 2 h. Then a solution of1-benzylpiperidin-4-one (30 g) in anhydrous tetrahydrofuran (100 ml) wasadded dropwise over 20 min at 40° C. and the mixture was stirredovernight at room temperature. Analysis by thin-layer chromatography:10% methanol in chloroform. The reaction mixture was hydrolysed at 0° C.with water (50 ml) and filtered over celite. It was extracted withdichloromethane (2×100 ml), the combined organic phases were washed withwater (50 ml), dried over sodium sulfate and concentrated to smallvolume under vacuum. The crude product was purified by columnchromatography (alox neutral) with 5% methanol in chloroform. Yield: 8.2g (19.3%)

(ii) (Apparatus: 1-l three-necked flask with cooler) Palladium on carbon(10%, catalytic amount) followed by ammonium formate solution (22.7 g in50 ml water) was added to a solution of1-benzyl-4-(pyridin-3-yl)piperidin-4-ol (32 g) in methanol (220 ml). Thereaction mixture was refluxed overnight at 68° C. Analysis by thin-layerchromatography: 20% methanol in chloroform. The mixture was filteredover celite and the filtrate concentrated to small volume under vacuum.The residue was washed with acetone (100 ml) in order to obtain thedesired compound in a clean state. Yield: 17.3 g (81.3%)

Amine F-20: 4-Pyridin-2-yl piperidin-4-ol

[50461-56-8] commercially available from e.g. Tyger Scientific.

Amine F-21: 1-Methyl-4-piperidin-4-yl piperazine

[436099-90-0] commercially available from e.g. ABCR.

Amine F-22: 1-[(1-Methyl-piperidin-4-yl)-methyl]piperazine

[735262-46-1] commercially available from e.g. Otava.

Amine F-23: 3-(4-Fluorophenyl)-3,8-diazaspiro[4.5]decan-4-onehydrochloride

(MDL No.: MFCD05861564) commercially available from e.g. ASW MedChem.

Amine F-24: 4-Piperidin-4-yloxypyridine hydrochloride

(i) tert-Butyl-4-hydroxypiperidine-1-carboxylate (6.348 g, 31.546 mmol)and triphenylphosphine (10.256 g, 39.432 mmol) were added to a solutionof 4-hydroxypyridine (3 g, 31.546 mmol) in tetrahydrofuran (50 ml) atroom temperature. Then diisopropyl azodicarboxylate (7.66 ml, 39.432mmol) was added dropwise and the mixture was then stirred for 15 h at55° C. Saturated sodium hydrogen carbonate solution (50 ml) was added tothe reaction mixture and it was extracted with ethyl acetate (4×80 ml).The combined organic phases were washed with saturated sodium chloridesolution (20 ml), dried (Na₂SO₄) and concentrated to small volume undervacuum. Then the crude product was purified by column chromatography(silica gel) with ethyl acetate/hexane (4:1). Yield: 4.11 g (46%)

(ii) Hydrogen chloride (47 ml, 59 mmol, 1.25 M solution in methanol) wasadded to a solution of tert-butyl4-(pyridin-3-yloxy)piperidine-1-carboxylate (4.1 g, 14.727 mmol) inmethanol (10 ml) at room temperature and the reaction mixture wasrefluxed for 30 min. The solvent was removed under vacuum and theresidue taken up in a little ethanol and mixed with diethyl ether. Thenthe mixture was cooled for 30 min in an ice bath and the solid that wasformed was filtered out and dried. Yield: 3.46 g (93%)

Amine F-25: 1-(4-Fluorophenyl)-3-methyl-3,8-diazaspiro[4.5]decan-4-onehydrochloride

(MDL No: MFCD08460813) commercially available from e.g. ASW MedChem.

Amine F-26: 3-[(4-Fluorophenyl)-methyl]-3,8-diazaspiro[4.5]decan-4-onehydrochloride

(MDL No: MFCD08461093) commercially available from e.g. ASW MedChem.

Amine F-27: 3-Benzyl-3,8-diazaspiro[4.5]decan-4-one hydrochloride

(MDL No: MFCD02179153) commercially available from e.g. ASW MedChem.

Amine F-28: 3-Benzyl-3,7-diazaspiro[4.4]nonane

(MDL No: MFCD04115133) commercially available from e.g. Tyger.

Amine F-29: 3-[4-(2-Pyrrolidin-1-yl-ethoxy)piperidin-4-yl]pyridinedihydrochloride

(i) n-Butyl lithium (2 eq.) was added to a solution of 3-bromopyridine(7.94 g, 1 eq.) in dry THF (1600 ml) at −70° C. and the mixture wasstirred at this temperature for 1 h. Then a solution of N-Boc piperidone(10 g, 1 eq.) in THF (400 ml) was added at −70° C. and the mixture wasstirred at this temperature for 2 h (DC control). On completion of thereaction the mixture was hydrolysed with saturated ammonium chloridesolution and then slowly heated to RT. It was diluted with ethylacetate. The organic phase was washed with sodium chloride solution anddried over sodium sulfate. The solvent was removed in a rotaryevaporator and the crude product obtained was purified by columnchromatography (silica gel, DCM/methanol, 9:1).

(ii) The alcohol (2 g) was dissolved in benzene (20 ml), mixed withsodium amide (10 eq.) at 25° C. and stirred at this temperature for 15min. Then 1-(2-chloroethyl)pyrrolidine (1.2 eq.) was added and themixture was refluxed for 16 h. On completion of the reaction (DCcontrol) the mixture was cooled to 0° C. and hydrolysed with ice. Theaqueous phase was extracted with ethyl acetate. The organic phase waswashed with water and saturated NaCl solution and dried over Na₂SO₄. Thesolvent was removed in a rotary evaporator and the crude productobtained was purified by column chromatography (silica gel,DCM/methanol, 95:5).

(iii) tert-Butyl4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-carboxylate(12.7 g, 33.82 mmol) was dissolved in methanol (80 ml), cooled in an icebath and mixed with acetyl chloride (12 ml, 169.1 mmol). After 3 h DCcontrol (dichloromethane/methanol 9/1) indicated that the reaction wascomplete; the solvent was removed under vacuum and the residue taken upin water/dichloromethane. The phases were separated, the aqueous phasewas washed with dichloromethane (twice) and freeze dried. Yield:quantitative

Amine F-30: 2-(Pyridin-4-yl-methyl)-2,5-diazabicyclo[2.2.1]heptanedihydrochloride

(i): tert-Butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (5 g,25.214 mmol) and pyridine-4-carbaldehyde (2.97 g, 27.74 mmol) wereintroduced into dichloromethane (650 ml), mixed with sodiumtriacetoxyboron hydride (10.6 g, 50.43 mmol) and glacial acetic acid(0.14 ml, 2.521 mmol) and the reaction mixture was stirred at roomtemperature for 15 h. The mixture was then hydrolysed with saturatedsodium hydrogen carbonate solution, the phases were separated and theaqueous phase was extracted twice with diethyl ether. The combinedorganic phases were washed with saturated sodium chloride solution,dried over magnesium sulfate and concentrated under vacuum. The crudeproduct was purified by column chromatography (silica gel;dichloromethane/methanol). Yield: 5.8 g, 79%

(ii): tert-Butyl5-(pyridin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (5.8g, 20.0 mmol) was dissolved in methanol (50 ml), cooled in an ice bathand mixed with acetyl chloride (7.1 ml). The reaction mixture wasstirred for 15 h at room temperature and then concentrated under reducedpressure. The residue was taken up in water, the aqueous phase waswashed twice with dichloromethane, frozen and the water removed byfreeze drying. Yield: 5.2 g, 99%

Amine F-31 was prepared from tert-butyl2,5-diazabicyclo[2.2.1]heptane-2-carboxylate by reacting it with thecorresponding aldehyde and then eliminating the protective group in amanner analogous to amine F-31.

Yield Amine Aldehyde (after 2 stages) 2-[(4-Fluorophenyl)methyl]-2,5-4-Fluoro- 77% diazabicyclo[2.2.1]heptane benzaldehyde dihydrochloride(F-31)

Amine F-32: (1-Pyridin-4-yl-piperidin-4-yl)amine dihydrochloride

(MDL No: MFCD06797043) commercially available from e.g. ABCR.

Amine F-33: 4-Phenyl-2,4,8-triazaspiro[4.5]decan-1-one

(MDL No: MFCD00005977) commercially available from e.g. ABCR.

Amine F-34:N-[[4-(4-Methylpiperazin-1-yl)-piperidin-4-yl]methyl]pyridine-4-carboxylicacid amide dihydrochloride

Stage 1: Water (1.2 ml), N-methylpiperazine (1 eq.), acetic acid (1 eq.)and KCN (1.1 eq.) were added to a methanolic solution (20 ml) ofN-benzyl piperidone (52.9 mmol). The reaction mixture was stirred for 1h at 25° C. and a solid was precipitated. 35% ammonium hydroxide (300ml) and ice (100 g) were then added to the batch. The solid was filteredout, washed repeatedly with water and then dried. Yield: 45%

Stage 2: A solution of concentrated H₂SO₄ (1.5 eq.) in THF (1 ml/mmol)was added dropwise to a cold (0° C.) suspension of LiAlH (3 eq.) in THF(2 ml/mmol) under an argon atmosphere (very exothermic). The suspensionwas stirred for 90 min at 25° C. and then cooled to 0° C. The cyanocomponent (1 eq.) in THF (2 ml/mmol) was added dropwise to this coldreaction mixture and on completion of the addition the mixture washeated for 12 h at 50° C. (DC control). The batch was carefully quenchedwith a saturated sodium sulfate solution and filtered through celite.The residue was washed with ethyl acetate, the organic phase was driedover sodium sulfate and concentrated to small volume under reducedpressure. The crude amine was obtained and was used directly in the nextstage with no further purification. Yield: 79%

Stage 3: TEA (5 eq.) and trifluoroacetic acid anhydride (2 eq.) wereadded to a solution of the amine from the second stage (74.5 mmol) indichloromethane (5 ml/mmol) at 0° C. The reaction mixture was stirredfor 2 h at 25° C. (DC control). It was diluted with dichloromethane,washed successively with water and saturated NaCl solution and driedover sodium sulfate. Concentration to small volume under reducedpressure resulted in the crude product, which was purified by columnchromatography (10% methanol in dichloromethane). Yield: 64%

Stage 4: A solution of the benzylated product from the third stage (19g) in methanol (285 ml) was degassed under argon. This was done byadding Pd(OH)₂ 10% (9.5 g) and AcOH (7.6 ml) and hydrogenating themixture for 16 h under normal pressure (DC and LCMS control). Themixture was filtered through celite, the residue washed with methanoland the combined organic phases evaporated to dryness under reducedpressure. The crude product that was obtained was used directly in thenext stage with no further purification. Yield: 14.8 g (quantitative)

Stage 5: DIPEA (1.5 eq.) and Boc anhydride (1.2 eq.) were added to asolution of the amine from the fourth stage (14.8 g, 48 mmol) indichloromethane (240 ml) at 0° C. The reaction mixture was stirred for 3h at room temperature. It was diluted with dichloromethane, washedsuccessively with water and saturated NaCl solution and dried oversodium sulfate. Concentration to small volume under reduced pressureresulted in the crude product, which was purified by columnchromatography (10% methanol in dichloromethane). Yield: 12.5 g (63%)

Stage 6: 1N NaOH (120 ml) was added to a solution of the Boc-protectedproduct from the fifth stage in methanol (80 ml) at 0° C. and thereaction mixture was stirred for 2 h at 25° C. (DC control). The mixturewas diluted with ethyl acetate, the aqueous phase was extractedrepeatedly with ethyl acetate and the combined organic phases werewashed with saturated NaCl solution. After drying over sodium sulfatethe organic phase was concentrated to small volume under reducedpressure and the crude product obtained was used directly in the nextstage with no further purification. Yield: 7.7 g (83%)

Stage 7: Triethylamine (2.5 eq.) and isonicotinoyl chloridehydrochloride (1 eq.) were added to a cold (0° C.) solution of the aminocomponent from the sixth stage (1 eq.) in dichloromethane. The reactionmixture was stirred for 2 h at 25° C. (DC control). The mixture wasquenched with crushed ice, diluted with dichloromethane and the organicphase was washed successively with water and saturated NaCl solution.After drying over sodium sulfate the organic phase was concentrated tosmall volume under reduced pressure and the crude product obtained waspurified by column chromatography (aluminium oxide neutral, methanol indichloromethane 1:9). Yield: 70%

Stage 8: HCl in dioxane (2M, 6 ml/mmol) was added to a solution of theBoc-protected product from the seventh stage in dioxane (2 ml/mmol) at0° C. and the reaction mixture was stirred for 3 h at 25° C. (DCcontrol). The precipitated solid was filtered out, washed with etherunder inert gas (very hygroscopic) and then dried under vacuum. Yield:80%

Amine F-35: 1-(Pyridin-2-yl-methyl)-[1,4]diazepan

[247118-06-5] available commercially from ChemCollect, for example.

Amine F-36: 4-Pyrrolidin-3-yl-pyridine

[150281-47-3] available commercially from Interchim, for example.

Amine F-37: piperazin-1-yl-pyridin-3-yl-methanone

[39640-08-9] available commercially from Fluorochem, for example.

Amine F-38: 8-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride

The synthesis was carried out analogously to the synthesis of amineF-14. To that end, tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylatewas reacted with 4-chloropyridinium chloride in stage (i) (yield: 22%).Then, in stage (ii), the Boc protecting group was removed. When thereaction was complete and the methanol had been removed under vacuum,the residue was taken up in ethanol and cooled, and acetone was added.The resulting suspension was stirred for 30 min in an ice bath, and theprecipitate was filtered out with suction, washed with acetone and driedunder vacuum (yield: 92%).

Amine F-39: 3-(Pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-enebis(2,2,2-trifluoroacetate) Stage (i): tert-Butyl4-methylenepiperidine-1-carboxylate

In a heated apparatus flushed with protecting gas,methyltriphenylphosphonium bromide (53.82 g, 150 mmol) was suspended indiethyl ether (300 ml) and cooled to 0° C. Potassium tert-butylate(15.78 g, 140 mmol) was added in portions, and the suspension wasstirred for 30 min. Boc-4-piperidone (20 g, 100 mmol), dissolved indiethyl ether (200 ml), was slowly added dropwise, and then the mixturewas heated to room temperature and stirred for 15 h. The reactionmixture was cooled, and ammonium chloride solution (300 ml, 10%) wasadded. After phase separation, the aqueous phase was extracted withether (3×200 ml), and the combined organic phases were dried (MgSO₄) andconcentrated under vacuum. The crude product was purified by columnchromatography (silica gel) with ether/hexane (1:1). Yield: 18.57 g(93%)

Stage (ii): tert-Butyl3-(pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate

(a): (Z)—N-Hydroxyisonicotinimidoyl chloride: Pyridine-4-carbaldoxime (1g, 8.19 mmol) was dissolved in DMF (10 ml); a solution ofN-chlorosuccinimide (1.31 g, 9.83 mmol) in DMF (5 ml) was slowly addeddropwise, and the reaction mixture was stirred at room temperature. Whenthe reaction was complete (monitoring by thin-layer chromatography, here6 h), diethyl ether (50 ml) and water (20 ml) were added, phaseseparation, extraction of the aqueous phase with diethyl ether (5×30ml). The combined organic phases were washed with water (50 ml) andsaturated sodium chloride solution (50 ml), dried (MgSO₄) andconcentrated under vacuum. The crude substance was reacted without beingpurified and analysed further. Yield: 0.74 g (100%)

(b): tert-Butyl-4-methylenepiperidine-1-carboxylate (0.7 g, 3.55 mmol)was dissolved in dichloromethane (10 ml) and dissolved to 0° C. underprotecting gas. (Z)—N-Hydroxyisonicotinimidoyl chloride (1.67 g, 10.64mmol), dissolved in dichloromethane (15 ml), was added, followed bytriethylamine (1.2 ml, 8.5 mmol) in dichloromethane (10 ml). Thereaction mixture was heated slowly to room temperature and stirred for15 h. It was diluted with dichloromethane (50 ml) and washed with water,10% citric acid and saturated sodium chloride solution (in each case 30ml), dried (MgSO₄) and concentrated under vacuum. The crude product waspurified by column chromatography (silica gel) with ethyl acetate/hexane10/1. Yield: 0.48 g (42%)

Stage (iii): 3-(Pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-enebis(2,2,2-trifluoroacetate)

tert-Butyl3-(pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate (0.48g, 1.5 mmol) was dissolved in dichloromethane (10 ml) and cooled, andtrifluoroacetic acid (1.2 ml, 15 mmol) was added slowly. After refluxingfor 2 h, the solvent was removed under vacuum and the residue wasco-evaporated with in each case 30 ml of toluene and methanol. Yield:0.74 g (100%)

Amine F-40:6-(Piperidin-1-ylmethyl)-2-(pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinolinetrihydrochloride Stage (i):2,2,2-Trifluoro-1-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone

2-(2,2,2-Trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carbaldehyde(2 g, 7.78 mmol) and piperidine (660 mg, 7.78 mmol) were dissolved in1,2-dichloroethane (24 ml), and sodium triacetoxyborohydride (2.29 g,10.89 mmol) was added. The reaction mixture was stirred for 15 h, thendiluted with dichloromethane, and sat. sodium hydrogen carbonatesolution (100 ml) was added. After phase separation, the aqueous phasewas extracted with dichloromethane (3×100 ml). The combined organicphases were washed with sat. sodium chloride solution (50 ml), driedover magnesium sulfate and concentrated under vacuum. The crude productwas purified by column chromatography (silica gel, ethylacetate/dichloromethane/methanol 10:1:1+ammonia solution (25% aq.)).Yield: 1.88 g (74%)

Stage (ii): 6-(Piperidin-1-ylmethyl)-1,2,3,4-tetrahydroisoquinolinedihydrochloride

2,2,2-Trifluoro-1-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone(1.88 g, 5.76 mmol) was dissolved in methanol (23 ml); potassiumcarbonate (1.99 g, 14.4 mmol) was added and the reaction mixture wasstirred for 15 h at RT. The solvent was then removed under vacuum, andthe residue was taken up in dichloromethane and washed with water (15ml). The aqueous phase was extracted with dichloromethane, and thecombined organic phases were dried over sodium sulfate and concentratedunder vacuum. The residue was taken up in an acetone/diethyl ethermixture, and the hydrochloride was precipitated with 2 M hydrogenchloride in diethyl ether (3 equiv.) and, after being filtered out withsuction, was dried under vacuum. Yield: 1.62 g (93%)

Stage (i): tert-Butyl3-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidine-1-carboxylate

6-(Piperidin-1-ylmethyl)-1,2,3,4-tetrahydroisoquinoline dihydrochloride(0.5 g, 1.65 mmol), triethylamine (0.57 ml, 4.12 mmol) and tert-butyl3-oxopyrrolidine-1-carboxylate (305 mg, 1.65 mmol) were dissolved in1,2-dichloroethane (13 ml), and sodium triacetoxyborohydride (480 mg,2.309 mmol) was added. The reaction mixture was stirred for 2 h, andthen sat. sodium hydrogen carbonate solution was added. After phaseseparation, the aqueous phase was extracted with dichloromethane (2×).The combined organic phases were washed with sat. sodium chloridesolution (1×), dried over magnesium sulfate and concentrated undervacuum. The crude product was purified by column chromatography (silicagel, ethyl acetate/methanol/ammonia (25% aq.) (200:20:1). Yield: 0.55 g(83%)

Stage (ii):6-(Piperidin-1-ylmethyl)-2-(pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinolinetrihydrochloride

1.25 M hydrogen chloride in methanol (11 ml) was added to tert-butyl3-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidine-1-carboxylate(0.55 g, 1.38 mmol), and the mixture was refluxed for 3 h. The solventwas removed under vacuum and the residue was taken up in ethanol/acetone(5 ml). Diethyl ether (20 ml) was then added, and the resultingprecipitate was filtered out and dried under vacuum. Yield: 0.41 g (73%)

Amine F-41: 2-(Pyridin-4-yl)-2,7-diazaspiro[4.4]nonane dihydrochloride

The synthesis was carried out analogously to the synthesis of amineF-14. To that end, tert-butyl 2,7-diazaspiro[4.4]nonane-2-carboxylatewas reacted with 4-chloropyridinium chloride in stage (i) (yield: 50%).Then, in stage (ii), the Boc protecting group was removed. When thereaction was complete and the methanol had been removed under vacuum,the residue was taken up in ethanol and cooled, and acetone was added.The resulting suspension was stirred for 30 min in an ice bath, and theprecipitate was filtered out with suction, washed with acetone and driedunder vacuum. (Yield: 73%).

Amine F-42: 9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochlorideStage (i): tert-Butyl9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (stage (iv)Amine-F43) (1 g, 3.74 mmol) and azetidine (0.25 ml, 3.74 mmol) wereplaced in 1,2-dichloroethane (15 ml), and sodium triacetoxyborohydride(1.1 g, 5.23 mmol) was added. The reaction mixture was stirred for 3 dat room temperature, and then saturated sodium hydrogen carbonatesolution was added. After phase separation, the aqueous phase wasextracted with dichloromethane (2×). The combined organic phases werewashed with saturated sodium chloride solution (1×), dried overmagnesium sulfate and concentrated under vacuum. The crude product waspurified by column chromatography (silica gel, ethylacetate/methanol/ammonia (25% aq.), 100:10:1). Yield: 1 g (89%)

Stage (ii): 9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane

Hydrogen chloride in methanol (1.25 mol/l, 15.5 ml) was added totert-butyl 9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1 g,3.24 mmol), and the mixture was refluxed for 45 min. The solvent wasremoved under vacuum and the residue was dissolved in a small amount ofethanol. A solid was then precipitated by addition of acetone, andfinally diethyl ether was added and the resulting precipitate wasfiltered out with suction. Yield: 0.87 g (95%)

Amine F-43: 9-(Pyridin-4-yloxy)-3-azaspiro[5.5]undecane dihydrochlorideStage (i): 1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid

To piperidine-4-carboxylic acid (25 g) in THF (75 ml) there was addedwater (75 ml), followed by sodium bicarbonate (30.8 g). The mixture wascooled to 0° C., and Cbz chloride (38.9 ml) was added dropwise. Thereaction mixture was then stirred for 5 h at room temperature (TLCmonitoring). When the reaction was complete, the organic solvent wasdistilled off and the residue was taken up in water (200 ml) and washedwith ethyl acetate (2×150 ml). The aqueous phase was acidified withdilute aqueous HCl solution and extracted with ethyl acetate. Theorganic phase was dried (Na₂SO₄) and concentrated under vacuum. Yield:48.5 g (96%)

Stage (ii): 1-Benzyl 4-methylpiperidine-1,4-dicarboxylate

1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid (48.5 g) in methanol(485 ml) was cooled to 0° C., and thionyl chloride (13.34 ml) was addeddropwise. The mixture was then refluxed for 20 min (TLC monitoring).When the reaction was complete, the methanol was distilled off and theresidue was taken up in water (15 ml) and with ethyl acetate (2×150 ml).The combined organic phases were extracted with water and sat. sodiumchloride solution, dried (Na₂SO₄) and concentrated under vacuum. Yield:38 g (67%)

Stage (iii): Benzyl 4-formylpiperidine-1-carboxylate

A solution of 1-benzyl 4-methylpiperidine-1,4-dicarboxylate (10 g) intoluene (100 ml), under nitrogen, was cooled to −78° C. Then DIBAL-H(60.9 ml) was added dropwise at −78° C., and the mixture was stirred for1 h at that temperature (TLC monitoring). Because the reaction wasincomplete, a further 0.2 eq. of DIBAL-H was added and stirring wascarried out for a further 30 min (TLC monitoring: some starting materialand the corresponding alcohol were detectable). Methanol (40 ml)followed by sat. sodium chloride solution (40 ml) were added slowly tothe reaction mixture at −78° C. The mixture was filtered over celite,and the solvent was removed under vacuum. The residue was extracted withethyl acetate (3×75 ml), dried (Na₂SO₄) and concentrated under vacuum.The crude product so obtained was purified by column chromatography(silica gel, 20% ethyl acetate/hexane). Yield: 4.3 g (49%)

Stage (iv): Benzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate

Methyl vinyl ketone (1.64 ml), ethanol (5 ml) and water (5 ml) wereadded to benzyl 4-formylpiperidine-1-carboxylate (5 g). The mixture wasthen added to a boiling solution of potassium hydroxide (0.22 g) inethanol (10 ml), and the resulting reaction mixture was refluxed for 1 h(TLC monitoring). When the reaction was complete, the mixture was addedto water (25 ml) and extracted with ethyl acetate (2×50 ml). Thecombined organic phases were dried (Na₂SO₄) and concentrated undervacuum. The crude product so obtained was purified by columnchromatography (silical gel, 25% ethyl acetate/hexane). Yield: 2.8 g(46%)

Stage (v): tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate

Boc anhydride (9.4 ml) and potassium carbonate (7.56 g) were added tobenzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (8.2 g) inEtOH/water (9:1) (200 ml). Pd/C (1 g) was then added, and the mixturewas subjected to hydrogenolysis for 4 h at 80 psi (TLC monitoring). Whenthe reaction was complete, the mixture was filtered over celite and thenrinsed with ethanol and ethyl acetate. The filtrate was dried (Na₂SO₄)and concentrated under vacuum. The residue was taken up in ethyl acetateand water, and the aqueous phase was extracted with ethyl acetate. Thecombined organic phases were dried (Na₂SO₄) and concentrated undervacuum. The crude product so obtained was purified by columnchromatography (silica gel, 20% ethyl acetate/hexane). Yield: 2.92 g,40%

Stage (vi): tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (1.5 g) wasdissolved in THF (7.5 ml) and cooled to −5° C. NaBH₄ (0.212 g) was thenadded and the mixture was stirred for 1 h at room temperature (TLCmonitoring). When the reaction was complete, acetic acid was added tothe mixture, and the methanol was then distilled off. The residue wastaken up in water (50 ml) and extracted with ethyl acetate (2×50 ml).The combined organic phases were dried (Na₂SO₄) and concentrated undervacuum. The crude product so obtained was purified by columnchromatography (silica gel, 30% ethyl acetate/hexane). Yield: 1.2 g(80%)

Stage (vii): tert-Butyl9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate

4-Chloropyridine hydrochloride (1.3 g) was added to sodium hydride (0.89g) in DMSO (20 ml), and the mixture was stirred for 10 min. tert-Butyl9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g) in DMSO (20 ml)was then added slowly, and the mixture was stirred overnight (TLCmonitoring: conversion about 30-35%). A catalytic amount of sodiumiodide was added, and the reaction mixture was stirred for 8 h at 80° C.(TLC monitoring). Methanol and NaHCO₃ solution were added to thereaction mixture, and stirring was carried out for 20 min. Extractionwith ethyl acetate was then carried out, followed by washing with NaHCO₃solution and cold water. The organic phase was dried (Na₂SO₄) andconcentrated under vacuum. The resulting crude product was purified bycolumn chromatography (silica gel, 70% ethyl acetate/hexane). Yield: 1.0g (40%)

Stage (viii): 9-(Pyridin-4-yloxy)-3-azaspiro[5.5]undecanedihydrochloride

tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate (1g, 2.886 mmol) was dissolved in methanol (2 ml); hydrogen chloride inmethanol (1.25 mol/l, 11.5 ml) was added, and the mixture was refluxedfor 30 min. The solvent was removed under vacuum and the residue wasdissolved in a small amount of ethanol. Acetone (about 25 ml) was thenadded, the mixture was stirred for 30 min at 0° C., and finally theresulting solid was filtered out with suction. Yield: 0.96 g (>99%)

Amine F-44: 9-(3,3-Difluoroazetidin-1-yl)-3-azaspiro[5.5]undecanedihydrochloride Stage (i): tert-Butyl9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (stage (iv)Amine-F43) (1 g, 3.74 mmol) was added to 3,3-difluoroazetidinehydrochloride (0.484 g, 3.74 mmol) and triethylamine (0.52 ml, 3.74mmol) in 1,2-dichloroethane (15 ml). The mixture was stirred for 5 min,and then sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was added andstirring was carried out for 3 d at room temperature. Saturated sodiumhydrogen carbonate solution was added and, after phase separation, theaqueous phase was extracted with dichloromethane (2×). The combinedorganic phases were washed with saturated sodium chloride solution (1×),dried over magnesium sulfate and concentrated under vacuum. Yield: 1.26g (98%)

Stage (ii): 9-(3,3-Difluoroazetidin-1-yl)-3-azaspiro[5.5]undecanedihydrochloride

tert-Butyl9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate(1.26 g, 3.66 mmol) was dissolved in hydrogen chloride in methanol (1.25mol/l, 29 ml) and refluxed for 45 min. The solvent was removed undervacuum and the residue was dissolved in a small amount of ethanol. Asolid was then precipitated by addition of acetone. The mixture wasstirred for 10 min at room temperature, then diethyl ether was added andstirring was carried out for a further 30 min at room temperature. Theresulting precipitate was filtered out with suction, washed with diethylether and dried under vacuum. Yield: 1.1 g (95%)

Amine F-45: Dimethyl-[4-(2-methylamino-ethyl)-1-phenyl-cyclohexyl]-aminedihydrochloride (F-45)

Stage 1:

A solution of triethyl phosphonoacetate (1.1 eq.) in THF (5 ml/mmol) wasadded slowly to a suspension, at 0° C., of 60% NaH (1 eq.) in dry THF (5ml/mmol). The resulting reaction mixture was stirred for 30 min at RT.It was then cooled to 0° C., and 1,4-dioxa-spiro[4.5]decan-8-one (1 eq.)in dry THF (5 ml/mmol) was added slowly at a constant temperature. Thereaction mixture was stirred for 16 h at 25° C. Quenching with ice andsat. sodium chloride solution was carried out, the aqueous phase wasextracted with ethyl acetate, and the organic phase was washedsuccessively with water and sodium chloride solution. The combined org.phases were dried over sodium sulfate and concentrated under reducedpressure. The crude product was purified by column chromatography (20%ethyl acetate in n-hexane).

Yield: 90

Stage 2:

A solution of the ester (1 eq.) obtained above in stage 1 in methanol (3ml/mmol) was deoxygenated with argon for 15 minutes, and then 10% Pd/C(50% by weight) was added. The resulting reaction mixture washydrogenated for 16 h under normal pressure and then filtered out overfiltering earth (celite). The residue was washed with methanol, and thecombined organic phases were concentrated completely. The crude productwas used immediately in the next stage without being purified further.Yield: 90% (crude product)

Stage 3:

A solution of the ester obtained in stage 2 (1 eq.) in THF (5 ml/mmol)was added slowly in the course of 30 minutes to a suspension, at 0° C.,of LAH (1 eq.) in dry THF (3 ml/mmol). When the addition was complete,the reaction mixture was stirred for 1 h at 25° C., cooled to 0° C. andquenched with sat. sodium sulfate solution and then filtered overcelite. After concentrating the solvent completely, the resulting crudeproduct was used in the next stage without being purified further.

Yield: 80% (crude product)

Stage 4:

Methanesulfonyl chloride (1.1 eq.) was added at 0° C., under a nitrogenatmosphere, to a solution of the alcohol obtained in stage 1 (1 eq.) inDCM (5 ml/mmol). When the addition was complete, the reaction mixturewas stirred for 2 h at 25° C. and diluted with dichloromethane, and theorganic phase was washed successively with water and sat. sodiumchloride solution and then dried over sodium sulfate. The organic phasewas concentrated under reduced pressure and the crude product was usedimmediately in the next stage.

Yield: 80% (crude product)

Stage 5:

2M methylamine solution in THF (10 ml) was added to a solution of thecompound obtained in stage 4 (5 mmol) in THF. The resulting reactionmixture was heated for 16 h at 100° C. in a firmly closed vessel. Thesolvent was then removed completely under reduced pressure and theresulting crude product, which could not be purified, was used in thenext stage.

Yield: 90% (crude product)

Stage 6:

Aqueous hydrochloric acid solution (6N, 2 ml/mmol) was added at 0° C. tothe amine obtained in stage 5 (1 eq.). The resulting reaction mixturewas stirred for 20 h at RT. Then the aqueous phase was washed with ethylacetate and subsequently adjusted to pH 14 with 6 N aqueous sodiumhydroxide solution. The aqueous phase was extracted with dichloromethaneand the combined organic phases were washed successively with water andsat. sodium chloride solution. The combined org. phases were dried oversodium sulfate, the solvent was concentrated under reduced pressure, andthe resulting crude product was used in the next stage without beingpurified further.

Yield: 80% (crude product)

Stage 7:

Diisopropylethylamine (2.5 eq.) and Boc₂(O) (1.2 eq.) were added at 0°C. to a solution of the amine obtained in stage 6 (1 eq.) indichloromethane (3 ml/mmol). When the addition was complete, the mixturewas stirred for 16 h at 25° C. The mixture was then diluted withdichloromethane, and the org. phase was washed successively with waterand sat. sodium chloride solution and finally dried over sodium sulfate.The org. phase was concentrated under reduced pressure, and the crudeproduct was purified by column chromatography (5% methanol indichloromethane).

Yield: 60%

Stage 8:

40% aqueous dimethylamine solution (71 ml) and acetic acid (26.5 ml) andKCN (1.5 eq.) were added at 0° C. to a solution of the Boc amineobtained in stage 7 (84.3 mmol) in methanol (45 ml). The resultingreaction mixture was stirred for 16 h at RT. Then 35% ammonium hydroxidesolution (300 ml) and ice (300 g) were added, the aqueous phase wasextracted with ethyl acetate, and the combined org. phases were washedsuccessively with water, sat. sodium chloride solution and aqueous ironsulfate solution. After drying over sodium sulfate, the org. phase wasconcentrated under reduced pressure. The crude product (25 g) was takenup in THF (50 ml), and phenylmagnesium bromide (337 ml, 1M in THF) wasadded at 0° C. When the addition was complete, the reaction mixture wasstirred for 16 h at 25° C. For working up, the reaction mixture wasquenched with sat. ammonium chloride solution and diluted with ethylacetate, and the org. phase was washed with sat. sodium chloridesolution. After drying over sodium sulfate, the org. phase wasconcentrated under reduced pressure and the resulting crude product waspurified by column chromatography (5% methanol in dichloromethane).

Yield: 40%

Stage 9:

HCl in dioxane (2M, 6 ml/mmol) was added at 0° C. to a dioxane solution(2 ml/mmol) of the Boc amine obtained in stage 8. The resulting reactionmixture was stirred for 3 h at 25° C., and the solid was filtered outunder protecting gas (very hygroscopic), washed with diethyl ether andfinally dried under a high vacuum.

Yield: 80%

Amine F-46: 1-[4-(3-Fluorophenyl)-piperidin-4-yl]-4-methyl-piperazinedihydrochloride (F-46)

1-[4-(3-Fluorophenyl)piperidin-4-yl]-4-methyl-piperazine dihydrochloride(F-46) was prepared analogously todimethyl-(4-phenyl-piperidin-4-yl)-amine dihydrochloride (F-07) usingmethylpiperazine and 3-fluorophenyl-magnesium bromide.

Amine F-47:2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl-methyl-aminetetrahydrochloride (F-47)

2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl-methyl-aminetetrahydrochloride (F-47) was prepared analogously todimethyl-[1-(3-methylamino-propyl)-4-phenyl-piperidin-4-yl]aminetrihydrochloride (F-11) using methylpiperazine and3-fluorophenylmagnesium bromide.

Amine F-48: Methyl-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-aminetrihydrochloride (F-48)

Stage 1:

An aqueous sodium dicarbonate solution (3.5 g in 57 ml of water) andsolid sodium chloride (7.5 g) were added at 0° C. to a suspension of3-chloropropylamine hydrochloride (38 mmol) in DCM (77 ml), and themixture was stirred for 30 minutes. A solution of Boc anhydride (1.2eq.) in dichloromethane (20 ml) was then slowly added dropwise. Thereaction mixture was stirred overnight at RT. The reaction mixture wasextracted with dichloromethane, and the org. phase was washed with waterand sat. sodium chloride solution, dried over sodium sulfate (anhydrous)and concentrated. The desired product was used in the next stage withoutbeing purified further.

Yield: 83.7%

Stage 2:

Methyl iodide (3 eq.) was added at 0° C. to a solution of the Boc amineobtained in stage 1 (155 mmol) in DMF (600 ml). Sodium hydride (2 eq.)was then added in portions. The reaction mixture was stirred for 15 h atRT. For working up, the reaction mixture was quenched with water andextracted with n-hexane. The combined org. phases were washed with waterand sat. sodium chloride solution, dried over sodium sulfate (anhydrous)and concentrated. The desired product was used in the next stage withoutbeing purified further.

Yield: quantitative

Stage 3:

DIPEA (2 eq.) and LiBr (1 eq.) were added to a solution of4-(4-pyridyl)-piperazine (30.64 mmol) and the Boc amine obtained instage 2 (1.5 eq.) in ethanol (150 ml). The reaction mixture was heatedfor 15 h at reflux and was then concentrated and diluted withdichloromethane and water. The org. phase was washed successively withwater and sat. sodium chloride solution, dried over sodium sulfate(anhydrous) and concentrated under reduced pressure. The residue waspurified by column chromatography over neutral alumina (eluant:DCM/MeOH) to yield the desired pure product.

Yield: 60%

Stage 4:

10 eq. of acetyl chloride were added at 0° C. to a solution of the Bocamine obtained in stage 3 in methanol. The progress of the reaction wasmonitored by means of thin-layer chromatography (10% MeOH/CHCl₃). Whenthe reaction was complete, the solvent was removed under reducedpressure and the product was obtained in the form of a solid.

TABLE 3 Amine overview Amine Structure Name F-01

Dimethyl-(3-piperazin-1-yl-propyl)amine (F-01) F-02

1-(1-Methyl-piperidin-4-yl) piperazine (F-02) F-03

3-(4-Ethyl-piperazin-1-yl)-propylamine (F-03) F-05

4-(2-Pyrrolidin-1-yl-ethyl) piperidine (F-05) F-07

Dimethyl-(4-phenyl-piperidin-4-yl)amine dihydrochloride (F-07) F-08

[1-(2-Aminoethyl)-4-thiophen-2-yl-piperidin-4-yl]- dimethylaminetrihydrochloride (F-08) F-09

Dimethyl-[1-(3-methylaminopropyl)-4-thiophen-2-yl- piperidin-4-yl]amine(F-09) F-10

Dimethyl-(4-thiophen-2-yl piperidin-4-yl)amine dihydrochloride (F-10)F-11

Dimethyl-[1-(3-methylaminopropyl)-4-phenyl piperidin-4- yl]aminetrihydrochloride (F-11) F-12

[4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]amine dihydrochloride (F-12) F-13

2-(1-Pyridin-4-yl-piperidin-4-yl)ethylamine dihydrochloride (F-13) F-14

3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane dihydrochloride (F-14) F-15

(1-Pyridin-4-yl-piperidin-4-yl)methylamine dihydrochloride (F-15) F-16

1-(4-Fluorophenyl)piperazine (F-16) F-17

2-Piperazin-1-yl pyrimidine (F-17) F-18

1-Pyridin-4-yl piperazine (F-18) F-19

4-Pyridin-3-yl piperidin-4-ol (F-19) F-20

4-Pyridin-2-yl piperidin-4-ol (F-20) F-21

1-Methyl-4-piperidin-4-yl piperazine (F-21) F-22

1-[(1-Methyl-piperidin-4-yl) methyl] piperazine (F-22) F-23

3-(4-Fluorophenyl)-3,8-diazaspiro[4.5]decan-4-one hydrochloride (F-23)F-24

4-Piperidin-4-yloxypyridine hydrochloride (F-24) F-25

1-(4-Fluorophenyl)-3-methyl-3,8-diazaspiro[4.5]decan-4- onehydrochloride (F-25) F-26

3-[(4-Fluorophenyl)-methyl]-3,8-diazaspiro[4.5]decan-4-one hydrochloride(F-26) F-27

3-Benzyl-3,8-diazaspiro[4.5]decan-4-one hydrochloride (F-27) F-28

3-Benzyl-3,7-diazaspiro[4.4]nonane (F-28) F-29

3-[4-(2-Pyrrolidin-1-yl-ethoxy-piperidin-4-yl]pyridine dihydrochloride(F-29) F-30

2-(Pyridin-4-yl-methyl)-2,5-diazabicyclo[2.2.1]heptane dihydrochloride(F-30) F-31

2-[(4-Fluorophenyl)methyl]-2,5-diazabicyclo[2.2.1]heptanedihydrochloride (F-31) F-32

(1-Pyridin-4-yl-piperidin-4-yl)amine dihydrochloride (F-32) F-33

4-Phenyl-2,4,8-triazaspiro[4.5]decan-1-one (F-33) F-34

N-[[4-(4-Methylpiperazin-1-yl)-piperidin-4-yl]methyl]pyridine-4-carboxylic acid amide dihydrochloride (F-34) F-35

1-(Pyridin-2-yl-methyl)-[1,4]diazepan (F-35) F-36

4-Pyrrolidin-3-yl-pyridine (F-36) F-37

Piperazin-1-yl-pyridin-3-yl-methanone (F-37) F-38

8-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (F-38) F-39

3-(Pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-enebis(trifluoroacetate) (F-39) F-40

6-(Piperidin-1-ylmethyl)-2-(pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline trihydrochloride (F-40) F-41

2-(Pyridin-4-yl)-2,7-diazaspiro[4.4]nonane dihydrochloride (F-41) F-42

9-(Azetldln-1-yl)-3-azaspiro[5.5]undecane dihydrochloride (F-42) F-43

9-(Pyridin-4-yloxy)-3-azaspiro[5.5]undecane dihydrochloride (F-43) F-44

9-(3,3-Difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride(F-44) F-45

Dimethyl-[4-(2-methylamino-ethyl)-1-phenyl-cyclohexyl]- aminedihydrochloride (F-45) F-46

1-[4-(3-Fluorophenyl)-piperidin-4-yl]-4-methyl-piperazinedihydrochloride (F-46) F-47

2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl-methyl-amine tetrahydrochloride (F-47) F-48

Methyl-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-amine trihydrochloride(F-48)

Syntheses of Individual Substances 6) Synthesis of Indolamides G

General Method for the Synthesis of Indolamides G

General procedure GP V—CU coupling: A solution of acid E (1 eq.) andcarbonyldiimidazole (2 eq.) in dichloromethane/dimethyl formamide wasstirred for 1 h at room temperature, then mixed with amine F (3 eq.)dissolved in dichloromethane and stirred for 12 h at room temperature.The reaction solution was washed 3 times with saturated sodium hydrogencarbonate solution, dried over magnesium sulfate and concentrated underreduced pressure. The desired product was obtained after purification bycolumn chromatography (alox neutral, ethyl acetate/hexane or silica,DCM/MeOH optionally NEt₃).

General procedure GP VI—EDCl coupling: A cold solution (0° C.) of acid E(1.5 eq.), HOBt (0.3 eq.) and diisopropylethylamine (4 eq.) indichloromethane was mixed with EDCI (1.5 eq.) and stirred for 15 min.Amine F (1 eq.) was then added and the mixture was stirred for 12 h atroom temperature. The reaction solution was washed 3 times with 0.5Npotassium hydroxide solution, dried over magnesium sulfate andconcentrated under reduced pressure. The desired product was obtainedafter purification by column chromatography (alox neutral, ethylacetate/hexane or silica, DCM/MeOH optionally NEt₃).

General procedure GP VII—CU coupling: 1,1′-Carbonyldiimidazole (1.05eq.) and carboxylic acid E (1 eq.) were dissolved in dichloromethane ora dichloromethane/N,N-dimethyl formamide (3:2) mixture and stirred for 1h at room temperature. Then amine F (optionally in the form of thecorresponding hydrochloride (xHCl)) (1.5 eq.) dissolved in a mixture ofdichloromethane/N,N-dimethyl formamide (3:2) and triethylamine (2-3 eq.)was added dropwise and the reaction mixture was stirred for 1 to 3 daysat room temperature (DC control). The mixture was mixed with a littlewater and concentrated to small volume under vacuum. Then the residuewas taken up in dichloromethane and washed with saturated sodiumhydrogen carbonate solution and saturated sodium chloride solution. Theaqueous phase was extracted with dichloromethane (twice) and thecombined organic phases were washed again with saturated sodium chloridesolution. Then the mixture was dried over sodium sulfate or magnesiumsulfate and concentrated to small volume under vacuum. The crude productwas purified by column chromatography (silica gel).

General procedure GP Va—TBTU coupling: The carboxylic acid E (1 equiv.),O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate(1 equiv.) and 1-hydroxybenzotriazole hydrate (1 equiv.) were placed intetrahydrofuran, under protecting gas, and the mixture was stirred for30 min at room temperature. A solution of the amine F (optionally in theform of the corresponding hydrochloride (xHCl) (1 equiv.) anddiisopropylethylamine (DIPEA) (3-5 equiv.) in tetrahydrofuran was added,and the reaction mixture was stirred for 15 h to 3 d at roomtemperature. Tetrahydrofuran was then removed under vacuum, the residuewas taken up in ethyl acetate or DCM and saturated sodium hydrogencarbonate solution, and the phases were separated. The aqueous phase wasextracted with ethyl acetate (or DCM), and the combined organic phaseswere in turn washed with sat. sodium chloride solution, dried oversodium sulfate and concentrated under vacuum. The crude product waspurified by column chromatography (silica gel) or by crystallization(from ethyl acetate).

General procedure GP Vb—HATU coupling: HATU (1.1 equiv.) was added to asolution of carboxylic acid E (1 equiv.) in THF, and the mixture wascooled to 0° C. DIPEA (2.5 equiv.) was added, and the reaction mixturewas stirred for 10 min. A solution of the amine F in THF was then addeddropwise, and the mixture was stirred for 16 h. Water was added andextraction with ethyl acetate was carried out (3×). The combined organicphases were extracted with water and sat. NaCl solution, dried overNa₂SO₄ and concentrated under vacuum. The crude product was purified bycolumn chromatography (silica gel).

General procedure GP Vc—EDCI coupling: DIPEA (2.4-4 equiv.), EDCI(1.2-1.5 equiv.) and HOBt (1.0-1.2 equiv.) were added to a solution, at0° C., of carboxylic acid E (1.0 equiv.) in DCM, and the resultingmixture was stirred for 15 min at 25° C. It was then cooled to 0° C.again, and the amine F (1 equiv.) in DCM (optionally plus DMF) wasadded. The reaction mixture was stirred for 16 h at 25° C. DCM wasadded, and the mixture was extracted with sodium bicarbonate solution,NH₄Cl solution, water and sat. NaCl solution, dried over Na₂SO₄ andconcentrated under vacuum. The crude product was purified by columnchromatography (silica gel).

Example no. Structure Name G-01

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]- benzenesulfonic acid amide (G-01)G-02

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl -1H-indol-7-yl]- benzenesulfonic acid amide (G-02)G-03

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyridin-4-yloxy-piperidin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide (G-03) G-04

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(1-oxo-4-phenyl-2,4,8-triazaspiro[4.5]decan-8-yl)-ethyl]-1H- indol-7-yl]-benzenesulfonic acidamide (G-04) G-05

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]- 1H-indol-7-yl]-benzenesulfonic acidamide (G-05) G-06

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]-1H- indol-7-yl]-benzenesulfonic acidamide (G-06) G-07

7-Chloro-2-[1-[3-oxo-3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- propyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one (G-07) G-08

7-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one (G-08) G-10

7-Chloro-2-[1-[3-oxo-3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- propyl]-1H-indol-7-yl]-2,3-dihydro-isoindol-1-one (G-10) G-11

7-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- ethyl]-1H-indol-7-yl]-2,3-dihydro-isoindol-1-one (G-11) G-12

7-Chloro-2-[1-[2-oxo-2-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decan-3-yl)-ethyl]-1H-indol-6-yl]-2,3-dihydro- isoindol-1-one (G-12) G-13

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(3-pyridin-4-yl-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)-ethyl]- 1H-indol-7-yl]-benzenesulfonicacid amide (G-13) G-14

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decan-3-yl)-ethyl]-1H- indol-7-yl]-benzenesulfonic acidamide (G-14) G-15

7-Chloro-2-[1-[2-oxo-2-(3-pyridin-4- yl-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)-ethyl]-1H-indol-6-yl]-2,3- dihydro-isoindol-1-one (G-15) G-16

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-[3-[6-(piperidin-1-yl-methyl)-1,2,3,4-tetrahydro-isoquinolin-2-yl]-pyrrolidin-1-yl]-ethyl]-1H-indol-7-yl]- benzenesulfonic acid amidedihydrochloride (G-16) G-17

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonan-3-yl)-ethyl]-1H- indol-7-yl]-benzenesulfonic acidamide (G-17) G-18

N-[1-[2-[9-(Azetidin-1-yl)-3- azaspiro[5.5]undecan-3-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6- dimethyl-benzenesulfonic acid amide(G-18) G-19

7-Chloro-2-[1-[2-oxo-2-(9-pyridin-4- yloxy-3-azaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-2,3-dihydro- isoindol-1-one (G-19) G-20

7-Chloro-2-[1-[2-[9-(3,3-difluoro- azetidin-1-yl)-3-azaspiro[5.5]undecan-3-yl]-2-oxo- ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one (G-20) G-21

2-[1-[2-[9-(Azetidin-1-yl)-3- azaspiro[5.5]undecan-3-yl]-2-oxo-ethyl]1H-indol-6-yl]-7-chloro-2,3- dihydro-isoindol-1-one (G-21) G-22

4-Methoxy-2,6-dimethyl-N-[1-[2-oxo- 2-(9-pyridin-4-yloxy-3-azaspiro[5.5]undecan-3-yl)-ethyl]- 1H-indol-7-yl]-benzenesulfonic acidamide (G-22) G-23

8-Chloro-4-methyl-2-[1-[2-oxo-2-(9- pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]- 1H-indol-6-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one (G-23) G-24

4-Methoxy-2,6-dimethyl-N-[[1-[2- oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]- 1H-indol-7-yl]-methyl]-benzenesulfonic acid amide (G-24) G-26

7-Methyl-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- ethyl]-1H-indol-6-yl]-2,3-dihydro-isoindol-1-one (G-26) G-27

5-Methyl-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)- ethyl]-1H-indol-6-yl]-1,2-dihydro-pyrrolo[2,1-e]imidazol-3-one (G-27) G-31

10-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-3,4-dihydro-2H- pyrazino[1,2-a]indol-1-one (G-31)G-33

8-Chloro-2-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-6-yl]-3,4-dihydro-2H- pyrrolo[1,2-a]pyrazin-1-one (G-33)Synthesised Example Analysis by/ no. Indole acid (E) Amine (F) Yield(LC/MS)^([1]) Comment G-01 2-[6-[[(4-Methoxy-2,6- 4-(2-Pyrrolidin-1-yl-43% R_(t) = 3.0 min; GP V dimethyl- ethyl) piperidine (F- (0.17 mmol)m/z = 553.2 phenyl)sulfonyl]amino]-1H- 05) [MH]⁺ indol-1-yl]acetic acid(E-03) G-02 2-[7-[[(4-Methoxy-2,6- 4-(2-Pyrrolidin-1-yl- 30% R_(t) = 3.3min; GP V dimethyl- ethyl) piperidine (F- (0.11 mmol) m/z = 553.2phenyl)sulfonyl]amino]-1H- 05) [MH]⁺ indol-1-yl]acetic acid (E-02) G-032-[7-[[(4-Methoxy-2,6- 4-Piperidin-4- 6% GP VII dimethyl- yloxypyridine(10 mg) phenyl)sulfonyl]amino]-1H- hydrochloride (F-24)indol-1-yl]acetic acid (E-02) G-04 2-[7-[[(4-Methoxy-2,6-4-Phenyl-2,4,8- 38% R_(t) = 5.2 min; GP V dimethyl-triazaspiro[4.5]decan- (2.0 mmol) m/z = 602.1 phenyl)sulfonyl]amino]-1H-1-one (F-33) [MH]⁺ indol-1-yl]acetic acid (E-02) G-052-[7-[[(4-Methoxy-2,6- 3-Pyridin-4-yl-3,9- 14% R_(t) = 3.6 min; GP VIIdimethyl- diazaspiro[5.5] (160 mgl) m/z = 602.1phenyl)sulfonyl]amino]-1H- undecane [MH]⁺ indol-1-yl]acetic acid (E-02)dihydrochloride (F-14) G-06 2-[7-[[(4-Methoxy-2,6- 3-[4-(2-Pyrrolidin-116% R_(t) = 2.8 min; GP VI dimethyl- ethoxy)piperidin-4-yl] (0.08 mmol)m/z = 646.1 phenyl)sulfonyl]amino]-1H- pyridine [MH]⁺ indol-1-yl]aceticacid (E-02) dihydrochloride (F-29) G-07 3-[6-(4-Chloro-3-oxo-1,2-3-Pyridin-4-yl-3,9- 44% R_(t) = 3.2 min; GP VIdihydro-isoindol-2-yl)-1H- diazaspiro[5.5] (0.16 mmol) m/z = 568.3indol-1-yl]propionic acid (E- undecane [MH]⁺ 15) dihydrochloride (F-14)G-08 2-[6-(4-Chloro-3-oxo-1,2- 3-Pyridin-4-yl-3,9- 54% R_(t) = 3.2 min;GP VI dihydro-isoindol-2-yl)-1H- diazaspiro[5.5] (0.21 mmol) m/z = 554.3indol-1-yl]acetic acid (E-16) undecane [MH]⁺ dihydrochloride (F-14) G-103-[7-(4-Chloro-3-oxo-1,2- 3-Pyridin-4-yl-3,9- 57% R_(t) = 3.2 min; GP VIdihydro-isoindol-2-yl)-1H- diazaspiro[5.5]- (0.24 mmol) m/z = 568.4indol-1-yl]-propionic acid undecane [MH]⁺ (E-17) dihydrochloride (F-14)G-11 2-[7-(4-Chloro-3-oxo-1,2- 3-Pyridin-4-yl-3,9-dihydro-isoindol-2-yl)-1H- diazaspiro[5.5]- 63 % R_(t) = 2.9 min; GP VIindol-1-yl]-acetic acid (E-19) undecane (0.27 mmol) m/z = 554.4dihydrochloride (F-14) [MH]⁺ G-12 2-[6-(4-Chloro-3-oxo-1,2-8-(Pyridin-4-yl)-2,8- 34% R_(t) = 3.1 min; GP Vadihydro-isoindol-2-yl)-1H- diazaspiro[4.5]decane (0.08 g) m/z = 540.2indol-1-yl]-acetic acid (E-16) dihydrochloride (F-38) [MH]⁺ G-132-[7-[[(4-Methoxy-2,6- 3-(Pyridin-4-yl)-1-oxa- 44% R_(t) = 34.2 GP Vadimethyl- 2,8-diazaspiro[4.5]- (0.1 g) min; phenyl)sulfonyl]amino]1Hdec-2-ene m/z = 588.3 indol-1-yl]-acetic acid (E-02)bis(trifluoroacetate) [MH]⁺ (F-39) G-14 2-[7-[[(4-Methoxy-2, 6-8-(Pyridin-4-yl)-2,8- 53% R_(t) = 3.5 min; GP Va dimethyl-diazaspiro[4.5]decane (0.12 g) m/z = 588.3 phenyl)sulfonyl]amino]-1H-dihydrochloride (F-38) [MH]⁺ indol-1-yl]-acetic acid (E-02) G-152-[6-(4-Chloro-3-oxo-1,2- 3-(Pyridin-4-yl)-1-oxa- 39% R_(t) = 3.7 min;GP Va dihydro-isoindol-2-yl)-1H- 2,8-diazaspiro[4.5]- (0.08 g) m/z =540.2 indol-1-yl]-acetic acid (E-16) dec-2-ene [MH]⁺bis(trifluoroacetate) (F-39) G-16 2-[7-[[(4-Methoxy-2, 6-6-(Piperidin-1- 74% R_(t) = 2.7 min; GP Va dimethyl- ylmethyl)-2- (0.14g) m/z = 670.4 phenyl)sulfonyl]amino]-1H- (pyrrolidin- [MH]⁺indol-1-yl]-acetic acid (E-02) 3-yl)-1,2,3,4- tetrahydroisoquinolinedihydrochloride (F-40) G-17 2-[7-[[(4-Methoxy-2,6- 2-(Pyridin-4-yl)-2,7-34% R_(t) = 3.5 min; GP Va dimethyl- diazaspiro[4.4]nonane (0.1 g) m/z =574.3 phenyl)sulfonyl]amino]-1H- dihydrochloride (F-41) [MH]⁺indol-1-yl]-acetic acid (E-02) G-18 2-[7-[[(4-Methoxy-2,6-9-(Azetidin-1-yl)-3- 29% R_(t) = 3.6 min; GP Va dimethyl- azaspiro[5.5]-(0.08 g) m/z = 579.4 phenyl)sulfonyl]amino]-1H- undecane [MH]⁺indol-1-yl]-acetic acid (E-02) dihydrochloride (F-42) G-192-[6-(4-Chloro-3-oxo-1,2- 9-(Pyridin-4-yloxy)-3- 72% R_(t) = 3.5 min; GPVa dihydro-isoindol-2-yl)-1H- azaspiro[5.5]- (0.3 g) m/z = 569.3indol-1-yl]-acetic acid (E-16) undecane [MH]⁺ dihydrochloride (F-43)G-20 2-[6-(4-Chloro-3-oxo-1,2- 9-(3,3- 39% R_(t) = 3.3 min; GP Vadihydro-isoindol-2-yl)-1H- Difluoroazetidin-1-yl)- (0.13 g) m/z = 567.3indol-1-yl]-acetic acid (E-16) 3-azaspiro[5.5]- [MH]⁺ undecanedihydrochloride (F-44) G-21 2-[6-(4-Chloro-3-oxo-1,2-9-(Azetidin-1-yl)-3- 51% R_(t) = 3.2 min; GP Vadihydro-isoindol-2-yl)-1H- azaspiro[5.5]- (0.15 g) m/z = 531.3indol-1-yl]-acetic acid (E-16) undecane [MH]⁺ dihydrochloride (F-42)G-22 2-[7-[[(4-Methoxy-2,6- 9-(Pyridin-4-yloxy)-3- 81% R_(t) = 3.8 min;GP Va dimethyl- azaspiro[5.5]- (0.32 g) m/z = 617.3phenyl)sulfonyl]amino]-1H- undecane [MH]⁺ indol-1-yl]-acetic acid (E-02)dihydrochloride (F-43) G-23 2-(6-(8-Chloro-4-methyl-1-3-Pyridin-4-yl-3,9- 40% R_(t) = 3.6 min; GP Vb oxopyrrolo[3,4-b]indol-diazaspiro[5.5]- m/z = 607.3 2(1H,3H,4H)-yl)-1H-indol-1 - undecane [MH]⁺yl)acetic acid (E-20) trifluoroacetate (F-14) G-24 R_(t) = 3.7 min; form/z = 616.5 synthesis [MH]⁺ see below G-26 2-(6-(7-Methyl-1-3-Pyridin-4-yl-3,9- 24% R_(t) = 3.6 min; GP Vcoxoisoindolin-2-yl)-1H-indol- diazaspiro[5.5]- m/z = 534.4 1-yl)aceticacid (E-21) undecane (F-14) [MH]⁺ G-27 2-(6-(5-Methyl-3-oxo-1H-3-Pyridin-4-yl-3,9- 30% R_(t) = 3.7 min; GP Vcpyrrolo[1,2-c]imidazol-2(3H)- diazaspiro[5.5]- m/z = 523.4yl)-1H-indol-1-yl)acetic acid undecane (F-14) [MH]⁺ (E-22) G-312-(6-(10-Chloro-1-oxo-3,4- 3-Pyridin-4-yl-3,9- 12% R_(t) = 3.7 min; GPVc dihydropyrazino[1,2-a]indol- diazaspiro[5.5]- m/z = 607.32(1H)-yl)-1H-indol-1- undecane (F-14) [MH]⁺ yl)acetic acid (E-23) G-332-(6-(8-Chloro-1-oxo-3,4- 3-Pyridin-4-yl-3,9- 25% R_(t) = 3.0 min; GP Vcdihydropyrrolo[1,2-a]pyrazin- diazaspiro[5.5]- m/z = 557.32(1H)-yl)-1H-indol-1- undecane (F-14) [MH]⁺ yl)acetic acid (E-24)^([1])Equipment and methods for HPLC-MS analysis: HPLC: Waters Alliance2795 with PDA Waters 2998; MS: Micromass Quattro Micro ™ API; column:Waters Atlantis ® T3, 3 μm, 100 Å, 2.1 × 30 mm; column temp: 40° C.,Eluent A: purified water +0.1% formic acid; Eluent B: acetonitrile(gradient grade) +0.1% formic acid; Gradient: 0% B to 100% B in 8.8 min,100% B for 0.4 min, 100% B to 0% B in 0.01 min, 0% B for 0.8 min; Flow:1.0 ml/min; Ionisation: ES+, 25 V; make up: 100 μl/min 70% methanol +0.2% formic acid; UV: 200 − 400 nm.

Exemplary compound G-24:4-Methoxy-2,6-dimethyl-N-[[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-7-yl]-methyl]-benzenesulfonicacid amide

Stage I: Ethyl 2-(7-cyano-1H-indol-1-yl)acetate

A solution of 1H-indole-7-carbonitrile (2.0 g, 14.08 mmol, 1.0 equiv.)in dry DMF (10 ml) was added at 0° C. to a suspension of NaH (0.845 g,21.12 mmol, 1.5 equiv. 60% in mineral oil) in DMF (10 ml), and themixture was stirred for 30 min. Ethyl bromoacetate (1.9 ml, 16.9 mmol,1.2 equiv.) was added at 0° C., and stirring was carried out for 1 h atRT. When the reaction was complete (TLC monitoring), the mixture wascooled and diluted with water (60 ml). Extraction with ethyl acetate(3×80 ml) was carried out, and the combined organic phases were washedwith sat. NaCl solution (2×100 ml), dried over Na₂SO₄ and concentratedunder vacuum. The crude product was purified by column chromatography(silica gel, 8-10% ethyl acetate/hexane) and the desired product wasisolated in the form of a yellow solid. Yield: 80% (2.6 g, 11.37 mmol)

Stage II: 2-(7-Cyano-1H-indol-1-yl)acetic acid

A solution of LiOH.H₂O (1.4 g, 34.06 mmol, 3.0 equiv.) in water (10 ml)was added at 0° C. to a solution of ethyl2-(7-cyano-1H-indol-1-yl)acetate (2.6 g, 11.37 mmol, 1.0 equiv.) in THF,and the mixture was stirred for 2 h at RT. When the reaction wascomplete (TLC monitoring), the mixture was concentrated under vacuum andthe residue was taken up in water (50 ml). Extraction with ethyl acetate(50 ml) was carried out, and then the aqueous phase was adjusted topH≈3-4 with 10% HCl solution. Extraction with DCM (2×50 ml) was thencarried out, and the combined organic phases were washed with sat. NaClsolution, dried over Na₂SO₄ and concentrated under vacuum. The desiredproduct was isolated in the form of a light-yellow solid.

Yield: 92% (2.1 g, 10.5 mmol)

Stage III: 2-(7-(Aminomethyl)-1H-indol-1-yl)acetic acid

Raney Ni (7.0 g) was added to a solution of2-(7-cyano-1H-indol-1-yl)acetic acid (700 mg, 3.5 mmol) in MeOH (15 ml),and the mixture was hydrogenated for 6 h at RT and 60 psi hydrogen in aParr apparatus. The reaction mixture was filtered over celite and thefiltrate was concentrated under vacuum. The crude product so obtainedwas used directly in the following stage without being purified further.Yield: 96% (692 mg, 3.36 mmol)

Stage IV: 2-(7-((tert-Butoxycarbonylamino)methyl)-1H-indol-1-yl)aceticacid

1 N NaOH (6 ml) was added at 0° C. to a solution of2-(7-(aminomethyl)-1H-indol-1-yl)acetic acid (692 mg, 3.36 mmol, 1.0equiv.) in dioxane, followed by (Boc)₂O (1.1 ml, 5.08 mmol, 1.5 equiv.).The resulting reaction mixture was stirred for 16 h at RT and then thesolvent was removed under vacuum. The residue was taken up in water (25ml) and extracted with ethyl acetate (2×20 ml). The aqueous phase wasthen adjusted to an acidic pH value with KHSO₄ solution at 0° C.Extraction with DCM (3×30 ml) was then carried out, and the combinedorganic phases were washed with sat. NaCl solution (40 ml), dried overNa₂SO₄ and concentrated under vacuum. The crude product so obtained wasused directly in the following stage without being purified further.

Yield: 36% (372 mg, 1.22 mmol)

Stage V: tert-Butyl(1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)methylcarbamate

HATU (464 mg, 1.22 mmol, 1.0 equiv.) and DIPEA (0.8 ml, 4.88 mmol, 4.0equiv.) were added at 0° C. to a suspension of2-(7-((tert-butoxycarbonylamino)methyl)-1H-indol-1-yl)acetic acid (372mg, 1.22 mmol, 1.0 equiv.) in THF (8 ml), and the mixture was stirredfor 15 min. A solution of 3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane(F-14) (283 mg, 1.22 mmol, 1.0 equiv.), dissolved in a mixture of THF (4ml) and DMF (0.5 ml), was added, and stirring was carried out for 14 hat RT. The reaction mixture was diluted with ethyl acetate (30 ml) andextracted with sodium bicarbonate solution (2×20 ml), NH₄Cl solution(2×20 ml), water (20 ml) and sat. NaCl solution (20 ml) and dried overNa₂SO₄. The solvent was removed under vacuum and the crude product waspurified by column chromatography (Alox neutral; 0.5% MeOH/DCM), and thedesired product was thus obtained in the form of a white solid.

Yield: 95% (600 mg, 1.16 mmol)

Stage VI:2-(7-(Aminomethyl)-1H-indol-1-yl)-1-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethanone

Dioxane-HCl (6 ml) was added to a solution of tert-butyl(1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)methylcarbamate(600 mg, 1.16 mmol, 1.0 equiv.) in dioxane (6 ml), and the mixture wasstirred for 1 h at RT. When the reaction was complete (TLC monitoring),the solvent was removed under vacuum and the residue was adjusted to abasic pH value with TEA and was concentrated again. The crude productwas purified by column chromatography (Alox neutral; 5-10% MeOH/DCM),and the desired product was thus obtained in the form of a white solid.

Yield: 45% (220 mg, 0.53 mmol)

Stage VII:4-Methoxy-2,6-dimethyl-N-((1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)methyl)benzenesulfonamide

A mixture of2-(7-(aminomethyl)-1H-indol-1-yl)-1-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethanone(220 mg, 0.53 mmol, 1.0 equiv.) and NaHCO₃ (134 mg, 1.59 mmol, 3.0equiv.) in THF-water(1:1, 20 ml) was added at 0° C. to a solution of2,6-dimethyl-4-methoxyphenylsulfonyl chloride (136 mg, 0.58 mmol, 1.1equiv.) in THF (5 ml), and the mixture was stirred for 16 h at RT. Thereaction mixture was diluted with water (15 ml) and extracted with ethylacetate (3×30 ml). The combined organic phases were washed with sat.NaCl solution (40 ml) and dried over Na₂SO₄. The solvent was removedunder vacuum and the crude product was purified by column chromatography(silica gel; 6-8% MeOH/DCM), and the desired product was thus obtainedin the form of a white solid.

Yield: 38% (64 mg, 0.104 mmol)

Library Syntheses

Parallel Method for the Synthesis of Indolamides G_Cc

The acid structural units E were reacted in a parallel synthesis withthe amines F to form the amides G_CC, as illustrated in the figureabove. The correlation between product and reagent, structural unit andmethod is shown in the synthesis matrix.

The crude products from the parallel synthesis were analysed byHPLC-MS^([2]) and then purified by Reverse Phase HPLC-MS^([2]). Theproducts were able to be identified by means of analytical HPLC-MSmeasurements^([3]). [2] Equipment and methods for HPLC-MS analysis:Parallel synthesis method: HPLC: Waters Alliance 2795 with PDA Waters2996; MS: ZQ 2000 MassLynx Single Quadrupol MS Detector; Column:Atlantis dC18 30×2.1 mm, 3 μm; Column temperature: 40° C., Eluent A:purified water+0.1% formic acid; Eluent B: acetonitrile (gradientgrade)+0.1% formic acid; Gradient: 0% B to 100% B in 2.3 min, 100% B for0.4 min, 100% B to 0% B in 0.01 min, 0% B for 0.8 min; Flow: 1.0 ml/min;Ionisation: ES+, 25V; make up: 100 μl/min 70% methanol+0.2% formic acid;UV: 200-400 nm.[3] Equipment and methods for HPLC-MS purification: PrepPump: Waters 2525; Make Up Pump: Waters 515; Auxiliary Detector: WatersDAD 2487; MS Detector: Waters Micromass ZQ; Injector/Fraction Collector:Waters Sample Manager 2767; Gradient: Initial: 60% Water 40%Methanol->12-14.5 min: 0% Water 100% Methanol->14.5-15 min: 60% Water40% Methanol; Flow: 35 ml/min Column: Macherey-Nagel, C18 Gravity,100×21 mm, 5μ.

Parallel Synthesis: Synthesis Instructions for the Preparation ofIndolamides G_CC

A solution of 1,1′-carbonyldiimidazole (200 μM) in 0.5 mldichloromethane was added to a solution of acid E (100 μM) in a mixtureof 1.8 ml dichloromethane and 0.2 ml DMF and the mixture is shaken for 1hour at room temperature. Then a solution^([4]) of amine F (200 μM) wasadded. The reaction mixture was shaken for 18 hours at room temperature.[4] The amines in the form of hydrochloride were mixed with a 0.5 Mexcess (relative to the hydrochloride) of Hünig's base and with 500 μlN,N-dimethyl formamide, then topped up to a total volume of 2 ml withdichloromethane, causing them to be dissolved or suspended. The aminesin the form of the free base were dissolved or suspended indichloromethane and/or N,N-dimethyl formamide.

3 ml of semi-saturated sodium hydrogen carbonate solution were added tothe reaction mixture and it was mixed intensively. The organic phase wasremoved and transferred to a tared vessel. Then the aqueous phase wasextracted once again with 3 ml dichloromethane. The combined organicphases were concentrated under reduced pressure in vacuum centrifuges(GeneVac). The final purification was performed by HPLC-MS^([3]). Thefinal analysis was performed by LC-MS^([2]).

Example Indole acid Amine no. Example name no. Indole acid name no.Amine name G_CC-1 4-Methoxy-2,6-dimethyl-N-[1-[2-[4- E-032-[6-[[(4-Methoxy-2,6- F-02 1-(1-Methyl-(1-methyl-piperidin-4-yl)-piperazin- dimethyl- piperidin-4-yl)1-yl]-2-oxo-ethyl]-1H-indol-6-yl]- phenyl)sulfonyl]amino]- piperazine(F-02) benzenesulfonic acid amide 1H-indol-1-yl] acetic acid (G_CC-1)(E-03) G_CC-2 4-Methoxy-2,6-dimethyl-N-[1-[2-[4- E-032-[6-[[(4-Methoxy-2,6- F-21 1-Methyl-4-piperidin-(4-methyl-piperazin-1-yl)-piperidin- dimethyl- 4-yl piperazine1-yl]-2-oxo-ethyl]-1H-indol-6-yl]- phenyl)sulfonyl]amino]- (F-21)benzenesulfonic acid amide 1H-indol-1-yl] acetic acid (G_CC-2) (E-03)G_CC-3 4-Methoxy-2,6-dimethyl-N-[1-[2- E-03 2-[6-[[(4-Methoxy-2,6- F-172-Piperazin-1-yl oxo-2-(4-pyrimidin-2-yl-piperazin-1- dimethyl-pyrimidine (F-17) yl)-ethyl]-1H-indol-6-yl]- phenyl)sulfonyl]amino]-benzenesulfonic acid amide 1H-indol-1-yl] acetic acid (G_CC-3) (E-03)G_CC-4 4-Methoxy-2,6-dimethyl-N-[1-[2-[4- E-03 2-[6-[[(4-Methoxy-2,6-F-22 1-[(1-Methyl- [(1-methyl-piperidin-4-yl)-methyl]- dimethyl-piperidin-4-yl) piperazin-1-yl]-2-oxo-ethyl]-1H- phenyl)sulfonyl]amino]-methyl] piperazine indol-6-yl]-benzenesulfonic acid 1H-indol-1-yl]acetic acid (F-22) amide (G_CC-4) (E-03) G_CC-5N-[1-[2-[4-(4-fluorophenyl)- E-02 2-[7-[[(4-Methoxy-2,6- F-161-(4-Fluoro- piperazin-1-yl]-2-oxo-ethyl]-1H- dimethyl-phenyl)piperazine indol-7-yl]-4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]- (F-16) benzenesulfonic acid amide 1H-indol-1-yl]acetic acid (G_CC-5) (E-02) G_CC-6 4-Methoxy-2,6-dimethyl-N-[1-[2- E-022-[7-[[(4-Methoxy-2,6- F-17 2-Piperazin-1-yloxo-2-(4-pyrimidin-2-yl-piperazin-1- dimethyl- pyrimidine (F-17)yl)-ethyl]-1H-indol-7-yl]- phenyl)sulfonyl]amino]- benzenesulfonic acidamide 1H-indol-1-yl] acetic acid (G_CC-6) (E-02) G_CC-74-Methoxy-2,6-dimethyl-N-[1-[2-[4- E-02 2-[7-[[(4-Methoxy-2,6- F-221-[(1-Methyl- [(1-methyl-piperidin-4-yl)-methyl]- dimethyl-piperidin-4-yl) piperazin-1-yl]-2-oxo-ethyl]-1H- phenyl)sulfonyl]amino]-methyl] piperazine indol-7-yl]-benzenesulfonic acid 1H-indol-1-yl]acetic acid (F-22) amide (G_CC-7) (E-02) G_CC-84-Chloro-2,5-dimethyl-N-[1-[2-[4- E-04 2-[6-[[(4-Chloro-2,5- F-221-[(1-Methyl- [(1-methyl-piperidin-4-yl)-methyl]- dimethyl-piperidin-4-yl) piperazin-1-yl]-2-oxo-ethyl]-1H- phenyl)sulfonyl]amino]-methyl] piperazine indol-6-yl]-benzenesulfonic acid 1H-indol-1-yl]acetic acid (F-22) amide (G_CC-8) (E-04) G_CC-92-[6-[[(4-Methoxy-2,6-dimethyl- E-03 2-[6-[[(4-Methoxy-2,6- F-15(1-Pyridin-4-yl- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-piperidin-4- yl]-N-[(1-pyridin-4-yl-piperidin-4-yl)-phenyl)sulfonyl]amino]- yl)methylamine methyl]-acetamide (G_CC-9)1H-indol-1-yl] acetic acid dihydrochloride (E-03) (F-15) G_CC-10N-[1-[2-(3-Benzyl-3,7- E-03 2-[6-[[(4-Methoxy-2,6- F-28 3-Benzyl-3,7-diazaspiro[4.4]nonan-7-yl)-2-oxo- dimethyl- diazaspiro[4.4]nonaneethyl]-1H-indol-6-yl]-4-methoxy-2,6- phenyl)sulfonyl]amino]- (F-28)dimethyl-benzenesulfonic acid 1H-indol-1-yl] acetic acid amide (G_CC-10)(E-03) G_CC-11 N-[3-(4-Dimethylamino-4-phenyl- E-032-[6-[[(4-Methoxy-2,6- F-11 Dimethyl-[1-(3-piperidin-1-yl)-propyl]-2-[6-[[(4- dimethyl- methylaminopropyl)-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- 4-phenyl piperidin-4-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl] acetic acid yl]amineyl]-N-methyl-acetamide (G_CC-11) (E-03) trihydrochloride (F-11) G_CC-12N-[1-[2-[3-(4-Fluorophenyl)-4-oxo- E-02 2-[7-[[(4-Methoxy-2,6- F-233-(4-Fluorophenyl)- 3,8-diazaspiro[4.5]decan-8-yl]-2- dimethyl- 3,8-oxo-ethyl]-1H-indol-7-yl]-4- phenyl)sulfonyl]amino]-diazaspiro[4.5]decan- methoxy-2,6-dimethyl- 1H-indol-1-yl] acetic acid4-one hydrochloride benzenesulfonic acid amide (E-02) (F-23) (G_CC-12)G_CC-13 N-[1-[2-(3-Benzyl-3,7- E-02 2-[7-[[(4-Methoxy-2,6- F-283-Benzyl-3,7- diazaspiro[4.4]nonan-7-yl)-2-oxo- dimethyl-diazaspiro[4.4]nonane ethyl]-1H-indol-7-yl]-4-methoxy-2,6-phenyl)sulfonyl]amino]- (F-28) dimethyl-benzenesulfonic acid1H-indol-1-yl] acetic acid amide (G_CC-13) (E-02) G_CC-14N-[3-(4-Dimethylamino-4-phenyl- E-02 2-[7-[[(4-Methoxy-2,6- F-11Dimethyl-[1-(3- piperidin-1-yl)-propyl]-2-[7-[[(4- dimethyl-methylaminopropyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-4-phenyl piperidin-4- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]acetic acid yl]amine yl]-N-methyl-acetamide (G_CC-14) (E-02)trihydrochloride (F-11) G_CC-15 2-[6-[[(4-Chloro-2,5-dimethyl- E-042-[6-[[(4-Chloro-2,5- F-11 Dimethyl-[1-(3-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- methylaminopropyl)-yl]-N-[3-(4-dimethylamino-4-phenyl- phenyl)sulfonyl]amino]- 4-phenylpiperidin-4- piperidin-1-yl)-propyl]-N-methyl- 1H-indol-1-yl] aceticacid yl]amine acetamide (G_CC-15) (E-04) trihydrochloride (F-11) G_CC-16N-[3-(4-Dimethylamino-4-phenyl- E-07 2-[7-[(Naphthalen-1- F-11Dimethyl-[1-(3- piperidin-1-yl)-propyl]-N-methyl-2-ylsulfonyl)amino]-1H- methylaminopropyl)-[7-[(naphthalen-1-ylsulfonyl)amino]- indol-1-yl] acetic acid 4-phenylpiperidin-4- 1H-indol-1-yl]-acetamide (E-07) yl]amine (G_CC-16)trihydrochloride (F-11) G_CC-17 N-[4-(Azetidin-1-yl)-4-phenyl- E-022-[7-[[(4-Methoxy-2,6- F-12 [4-(Azetidin-1-yl)-4-cyclohexyl]-2-[7-[[(4-methoxy-2,6- dimethyl- phenyl-dimethyl-phenyl)sulfonyl]amino]- phenyl)sulfonyl]amino]-cyclohexyl]amine 1H-indol-1-yl]-acetamide 1H-indol-1-yl] acetic aciddihydrochloride (G_CC-17) (E-02) (F-12) G_CC-18N-[3-(4-Dimethylamino-4-thiophen- E-02 2-[7-[[(4-Methoxy-2,6- F-09Dimethyl-[1-(3- 2-yl-piperidin-1-yl)-propyl]-2-[7-[[(4- dimethyl-methylaminopropyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-4-thiophen-2-yl- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]acetic acid piperidin-4-yl]amine yl]-N-methyl-acetamide (G_CC-18) (E-02)(F-09) G_CC-19 N-[2-(4-Dimethylamino-4-thiophen- E-022-[7-[[(4-Methoxy-2,6- F-08 [1-(2-Aminoethyl)-4-2-yl-piperidin-1-yl)-ethyl]-2-[7-[[(4- dimethyl- thiophen-2-yl-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- piperidin-4-yl]-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl] acetic aciddimethylamine yl]-acetamide (G_CC-19) (E-02) trihydrochloride (F-08)G_CC-20 N-[1-[2-(4-Dimethylamino-4- E-02 2-[7-[[(4-Methoxy-2,6- F-10Dimethyl-(4- thiophen-2-yl-piperidin-1-yl)-2-oxo- dimethyl-thiophen-2-yl ethyl]-1H-indol-7-yl]-4-methoxy-2,6-phenyl)sulfonyl]amino]- piperidin-4-yl)amine dimethyl-benzenesulfonicacid 1H-indol-1-yl] acetic acid dihydrochloride amide (G_CC-20) (E-02)(F-10) G_CC-21 2-[7-[[(4-Methoxy-2,6-dimethyl- E-022-[7-[[(4-Methoxy-2,6- F-13 2-(1-Pyridin-4-yl-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- piperidin-4-yl]-N-[2-(1-pyridin-4-yl-piperidin-4- phenyl)sulfonyl]amino]-yl)ethylamine yl)-ethyl]-acetamide (G_CC-21) 1H-indol-1-yl] acetic aciddihydrochloride (E-02) (F-13) G_CC-22 N-[2-(4-Dimethylamino-4-thiophen-E-05 3-[6-[[(4-Methoxy-2,6- F-08 [1-(2-Aminoethyl)-4-2-yl-piperidin-1-yl)-ethyl]-3-[6-[[(4- dimethyl- thiophen-2-yl-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- piperidin-4-yl]-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl] propionicdimethylamine yl]-propionamide (G_CC-22) acid (E-05) trihydrochloride(F-08) G_CC-23 3-[6-[[(4-Methoxy-2,6-dimethyl- E-053-[6-[[(4-Methoxy-2,6- F-13 2-(1-Pyridin-4-yl-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- piperidin-4-yl]-N-[2-(1-pyridin-4-yl-piperidin-4- phenyl)sulfonyl]amino]-yl)ethylamine yl)-ethyl]-propionamide (G_CC-23) 1H-indol-1-yl] propionicdihydrochloride acid (E-05) (F-13) G_CC-242-[6-[[(4-Chloro-2,5-dimethyl- E-04 2-[6-[[(4-Chloro-2,5- F-132-(1-Pyridin-4-yl- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-piperidin-4- yl]-N-[2-(1-pyridin-4-yl-piperidin-4-phenyl)sulfonyl]amino]- yl)ethylamine yl)-ethyl]-acetamide (G_CC-24)1H-indol-1-yl] acetic acid dihydrochloride (E-04) (F-13) G_CC-25N-[3-(4-Dimethylamino-4-thiophen- E-07 2-[7-[(Naphthalen-1- F-09Dimethyl-[1-(3- 2-yl-piperidin-1-yl)-propyl]-N- ylsulfonyl)amino]-1H-methylaminopropyl)- methyl-2-[7-[(naphthalen-1- indol-1-yl] acetic acid4-thiophen-2-yl- ylsulfonyl)amino]-1H-indol-1-yl]- (E-07)piperidin-4-yl]amine acetamide (G_CC-25) (F-09) G_CC-262-[7-[[(4-Chloro-2,5-dimethyl- E-08 2-[7-[[(4-Chloro-2,5- F-09Dimethyl-[1-(3- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-methylaminopropyl)- yl]-N-[3-(4-dimethylamino-4- phenyl)sulfonyl]amino]-4-thiophen-2-yl- thiophen-2-yl-piperidin-1-yl)-propyl]- 1H-indol-1-yl]acetic acid piperidin-4-yl]amine N-methyl-acetamide (G_CC-26) (E-08)(F-09) G_CC-27 2-[7-[[(4-Chloro-2,5-dimethyl- E-08 2-[7-[[(4-Chloro-2,5-F-08 [1-(2-Aminoethyl)-4- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-thiophen-2-yl- yl]-N-[2-(4-dimethylamino-4- phenyl)sulfonyl]amino]-piperidin-4-yl]- thiophen-2-yl-piperidin-1-yl)-ethyl]- 1H-indol-1-yl]acetic acid dimethylamine acetamide (G_CC-27) (E-08) trihydrochloride(F-08) G_CC-28 2-[7-[[(4-Chloro-2,5-dimethyl- E-08 2-[7-[[(4-Chloro-2,5-F-13 2-(1-Pyridin-4-yl- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-piperidin-4- yl]-N-[2-(1-pyridin-4-yl-piperidin-4-phenyl)sulfonyl]amino]- yl)ethylamine yl)-ethyl]-acetamide (G_CC-28)1H-indol-1-yl] acetic acid dihydrochloride (E-08) (F-13) G_CC-29N-[3-(4-Dimethylamino-4-thiophen- E-03 2-[6-[[(4-Methoxy-2,6- F-09Dimethyl-[1-(3- 2-yl-piperidin-1-yl)-propyl]-2-[6-[[(4- dimethyl-methylaminopropyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-4-thiophen-2-yl- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]acetic acid piperidin-4-yl]amine yl]-N-methyl-acetamide (G_CC-29) (E-03)(F-09) G_CC-30 N-[2-(4-Dimethylamino-4-thiophen- E-032-[6-[[(4-Methoxy-2,6- F-08 [1-(2-Aminoethyl)-4-2-yl-piperidin-1-yl)-ethyl]-2-[6-[[(4- dimethyl- thiophen-2-yl-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- piperidin-4-yl]-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl] acetic aciddimethylamine yl]-acetamide (G_CC-30) (E-03) trihydrochloride (F-08)G_CC-31 N-[1-[2-[1-(4-Fluorophenyl)-3- E-02 2-[7-[[(4-Methoxy-2,6- F-251-(4-Fluorophenyl)- methyl-4-oxo-3,8- dimethyl- 3-methyl-3,8-diazaspiro[4.5]decan-8-yl]-2-oxo- phenyl)sulfonyl]amino]-diazaspiro[4.5]decan- ethyl]-1H-indol-7-yl]-4-methoxy-2,6-1H-indol-1-yl] acetic acid 4-one hydrochloride dimethyl-benzenesulfonicacid (E-02) (F-25) amide (G_CC-31) G_CC-32 N-[1-[2-(3-Benzyl-4-oxo-3,8-E-02 2-[7-[[(4-Methoxy-2,6- F-27 3-Benzyl-3,8-diazaspiro[4.5]decan-8-yl)-2-oxo- dimethyl- diazaspiro[4.5]decan-ethyl]-1H-indol-7-yl]-4-methoxy-2,6- phenyl)sulfonyl]amino]- 4-onehydrochloride dimethyl-benzenesulfonic acid 1H-indol-1-yl] acetic acid(F-27) amide (G_CC-32) (E-02) G_CC-33 N-[1-[2-[2-[(4-Fluorophenyl)- E-032-[6-[[(4-Methoxy-2,6- F-31 2-[(4-Fluoro- methyl]-2,5- dimethyl-phenyl)methyl]-2,5- diazabicyclo[2.2.1]heptan-5-yl]-2-phenyl)sulfonyl]amino]- diazabicyclo[2.2.1]heptaneoxo-ethyl]-1H-indol-6-yl]-4- 1H-indol-1-yl] acetic acid dihydrochloridemethoxy-2,6-dimethyl- (E-03) (F-31) benzenesulfonic acid amide (G_CC-33)G_CC-34 4-Methoxy-2,6-dimethyl-N-[1-[2- E-02 2-[7-[[(4-Methoxy-2,6- F-302-(Pyridin-4-yl-methyl)-2,5- oxo-2-[2-(pyridin-4-yl-methyl)-2,5-dimethyl- diazabicyclo[2.2.1]heptane diazabicyclo[2.2.1]heptan-5-yl]-phenyl)sulfonyl]amino]- dihydrochloride ethyl]-1H-indol-7-yl]-1H-indol-1-yl] acetic acid (F-30) benzenesulfonic acid amide (E-02)(G_CC-34) G_CC-35 4-Methoxy-2,6-dimethyl-N-[1-[3- E-053-[6-[[(4-Methoxy-2,6- F-14 3-Pyridin-4-yl-3,9-oxo-3-(3-pyridin-4-yl-3,9- dimethyl- diazaspiro[5.5]undecanediazaspiro[5.5]undecan-9-yl)- phenyl)sulfonyl]amino]- dihydrochloridepropyl]-1H-indol-6-yl]- 1H-indol-1-yl] propionic (F-14) benzenesulfonicacid amide acid (E-05) (G_CC-35) G_CC-364-Chloro-2,5-dimethyl-N-[1-[2-oxo- E-04 2-[6-[[(4-Chloro-2,5- F-143-Pyridin-4-yl-3,9- 2-(3-pyridin-4-yl-3,9- dimethyl-diazaspiro[5.5]undecane diazaspiro[5.5]undecan-9-yl)-ethyl]-phenyl)sulfonyl]amino]- dihydrochloride 1H-indol-6-yl]-benzenesulfonicacid 1H-indol-1-yl] acetic acid (F-14) amide (G_CC-36) (E-04) G_CC-37N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9- E-06 2-[6-[[[2-(Trifluoromethyl)-F-14 3-Pyridin-4-yl-3,9- diazaspiro[5.5]undecan-9-yl)-ethyl]-phenyl]sulfonyl]amino]- diazaspiro[5.5]undecane1H-indol-6-yl]-2-(trifluoromethyl)- 1H-indol-1-yl] acetic aciddihydrochloride benzenesulfonic acid amide (E-06) (F-14) (G_CC-37)G_CC-38 N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9- E-07 2-[7-[(Naphthalen-1-F-14 3-Pyridin-4-yl-3,9- diazaspiro[5.5]undecan-9-yl)-ethyl]-ylsulfonyl)amino]-1H- diazaspiro[5.5]undecane1H-indol-7-yl]-naphthalene-1- indol-1-yl] acetic acid dihydrochloridesulfonic acid amide (G_CC-38) (E-07) (F-14) G_CC-394-Chloro-2,5-dimethyl-N-[1-[2-oxo- E-08 2-[7-[[(4-Chloro-2,5- F-143-Pyridin-4-yl-3,9- 2-(3-pyridin-4-yl-3,9- dimethyl-diazaspiro[5.5]undecane diazaspiro[5.5]undecan-9-yl)-ethyl]-phenyl)sulfonyl]amino]- dihydrochloride 1H-indol-7-yl]-benzenesulfonicacid 1H-indol-1-yl] acetic acid (F-14) amide (G_CC-39) (E-08) G_CC-404-Methoxy-2,6-dimethyl-N-[1-[3-[4- E-14 3-[7-[[(4-Methoxy-2,6- F-021-(1-Methyl- (1-methyl-piperidin-4-yl)-piperazin- dimethyl-piperidin-4-yl) 1-yl]-3-oxo-propyl]-1H-indol-7-yl]-phenyl)sulfonyl]amino]- piperazine (F-02) benzenesulfonic acid amide1H-indol-1-yl] propionic (G_CC-40) acid (E-14) G_CC-414-Methoxy-2,6-dimethyl-N-[1-[3- E-14 3-[7-[[(4-Methoxy-2,6- F-054-(2-Pyrrolidin-1-yl- oxo-3-[4-(2-pyrrolidin-1-yl-ethyl)- dimethyl-ethyl) piperidine piperidin-1-yl]-propyl]-1H-indol-7-phenyl)sulfonyl]amino]- (F-05) yl]-benzenesulfonic acid amide1H-indol-1-yl] propionic (G_CC-41) acid (E-14) G_CC-424-Methoxy-2,6-dimethyl-N-[1-[3-[4- E-14 3-[7-[[(4-Methoxy-2,6- F-211-Methyl-4-piperidin- (4-methyl-piperazin-1-yl)-piperidin- dimethyl-4-yl piperazine 1-yl]-3-oxo-propyl]-1H-indol-7-yl]-phenyl)sulfonyl]amino]- (F-21) benzenesulfonic acid amide 1H-indol-1-yl]propionic (G_CC-42) acid (E-14) G_CC-434-Methoxy-2,6-dimethyl-N-[1-[3-[4- E-14 3-[7-[[(4-Methoxy-2,6- F-221-[(1-Methyl- [(1-methyl-piperidin-4-yl)-methyl]- dimethyl-piperidin-4-yl) piperazin-1-yl]-3-oxo-propyl]-1H-phenyl)sulfonyl]amino]- methyl] piperazine indol-7-yl]-benzenesulfonicacid 1H-indol-1-yl] propionic (F-22) amide (G_CC-43) acid (E-14) G_CC-44N-[1-[3-[4-(3-Dimethylamino- E-14 3-[7-[[(4-Methoxy-2,6- F-01Dimethyl-(3- propyl)-piperazin-1-yl]-3-oxo- dimethyl- piperazin-1-yl-propyl]-1H-indol-7-yl]-4-methoxy- phenyl)sulfonyl]amino]- propyl)amine(F-01) 2,6-dimethyl-benzenesulfonic acid 1H-indol-1-yl] propionic amide(G_CC-44) acid (E-14) G_CC-45 N-[1-[3-(4-Hydroxy-4-pyridin-2-yl- E-143-[7-[[(4-Methoxy-2,6- F-20 4-Pyridin-2-ylpiperidin-1-yl)-3-oxo-propyl]-1H- dimethyl- piperidin-4-ol (F-20)indol-7-yl]-4-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-benzenesulfonic acid amide 1H-indol-1-yl] propionic (G_CC-45) acid(E-14) G_CC-46 N-[3-(4-Dimethylamino-4-thiophen- E-143-[7-[[(4-Methoxy-2,6- F-09 Dimethyl-[1-(3-2-yl-piperidin-1-yl)-propyl]-3-[7-[[(4- dimethyl- methylaminopropyl)-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- 4-thiophen-2-yl-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl] propionicpiperidin-4-yl]amine yl]-N-methyl-propionamide acid (E-14) (F-09)(G_CC-46) G_CC-47 3-[7-[[(4-Methoxy-2,6-dimethyl- E-143-[7-[[(4-Methoxy-2,6- F-13 2-(1-Pyridin-4-yl-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- piperidin-4-yl]-N-[2-(1-pyridin-4-yl-piperidin-4- phenyl)sulfonyl]amino]-yl)ethylamine yl)-ethyl]-propionamide (G_CC-47) 1H-indol-1-yl] propionicdihydrochloride acid (E-14) (F-13) G_CC-48N-[1-[3-(4-Dimethylamino-4-phenyl- E-14 3-[7-[[(4-Methoxy-2,6- F-07Dimethyl-(4-phenyl- piperidin-1-yl)-3-oxo-propyl]-1H- dimethyl-piperidin-4-yl)amine indol-7-yl]-4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]- dihydrochloride benzenesulfonic acid amide1H-indol-1-yl] propionic (F-07) (G_CC-48) acid (E-14) G_CC-49N-[3-(4-Dimethylamino-4-phenyl- E-14 3-[7-[[(4-Methoxy-2,6- F-11Dimethyl-[1-(3- piperidin-1-yl)-propyl]-3-[7-[[(4- dimethyl-methylaminopropyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-4-phenyl piperidin-4- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]propionic yl]amine yl]-N-methyl-propionamide acid (E-14)trihydrochloride (G_CC-49) (F-11) G_CC-50 N-[4-(Azetidin-1-yl)-4-phenyl-E-14 3-[7-[[(4-Methoxy-2,6- F-12 [4-(Azetidin-1-yl)-4-cyclohexyl]-3-[7-[[(4-methoxy-2,6- dimethyl- phenyl-dimethyl-phenyl)sulfonyl]amino]- phenyl)sulfonyl]amino]-cyclohexyl]amine 1H-indol-1-yl]-propionamide 1H-indol-1-yl] propionicdihydrochloride (G_CC-50) acid (E-14) (F-12) G_CC-51N-[2-(4-Dimethylamino-4-thiophen- E-14 3-[7-[[(4-Methoxy-2,6- F-08[1-(2-Aminoethyl)-4- 2-yl-piperidin-1-yl)-ethyl]-3-[7-[[(4- dimethyl-thiophen-2-yl- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-piperidin-4-yl]- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]propionic dimethylamine yl]-propionamide (G_CC-51) acid (E-14)trihydrochloride (F-08) G_CC-52 N-[1-[3-Oxo-3-(3-pyridin-4-yl-3,9- E-093-[7-[[[2-(Trifluoromethyl)- F-14 3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)- phenyl]sulfonyl]amino]-diazaspiro[5.5]undecane propyl]-1H-indol-7-yl]-2- 1H-indol-1-yl]propionic dihydrochloride (trifluoromethyl)-benzenesulfonic acid (E-09)(F-14) acid amide (G_CC-52) G_CC-53 N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-E-13 2-[7-[[[2-(Trifluoromethyl)- F-14 3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]- phenyl]sulfonyl]amino]-diazaspiro[5.5]undecane 1H-indol-7-yl]-2-(trifluoromethyl)-1H-indol-1-yl] acetic acid dihydrochloride benzenesulfonic acid amide(E-13) (F-14) (G_CC-53) G_CC-54 4-Methoxy-2,6-dimethyl-N-[1-[3- E-143-[7-[[(4-Methoxy-2,6- F-14 3-Pyridin-4-yl-3,9-oxo-3-(3-pyridin-4-yl-3,9- dimethyl- diazaspiro[5.5]undecanediazaspiro[5.5]undecan-9-yl)- phenyl)sulfonyl]amino]- dihydrochloridepropyl]-1H-indol-7-yl]- 1H-indol-1-yl] propionic (F-14) benzenesulfonicacid amide acid (E-14) (G_CC-54) G_CC-56 N-[3-(4-Ethyl-piperazin-1-yl)-E-14 3-[7-[[(4-Methoxy-2,6- F-03 3-(4-Ethyl-piperazin-propyl]-3-[7-[[(4-methoxy-2,6- dimethyl- 1-yl)-propylaminedimethyl-phenyl)sulfonyl]amino]- phenyl)sulfonyl]amino]- (F-03)1H-indol-1-yl]-propionamide 1H-indol-1-yl] propionic (G_CC-56) acid(E-14) G_CC-57 4-Methoxy-2,6-dimethyl-N-[1-[2- E-032-[6-[[(4-Methoxy-2,6- F-29 3-[4-(2-Pyrrolidin-1-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin- dimethyl- yl-ethoxy)piperidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]- phenyl)sulfonyl]amino]- 4-yl]pyridine 1H-indol-6-yl]-benzenesulfonic acid 1H-indol-1-yl] acetic aciddihydrochloride amide (G-CC-57) (E-03) (F-29) G_CC-594-Chloro-2,5-dimethyl-N-[1-[3-[4-(1- E-10 3-[7-[[(4-Chloro-2,5- F-021-(1-Methyl- methyl-piperidin-4-yl)-piperazin-1- dimethyl-piperidin-4-yl) yl]-3-oxo-propyl]-1H-indol-7-yl]-phenyl)sulfonyl]amino]- piperazine (F-02) benzenesulfonic acid amide1H-indol-1-yl] propionic (G_CC-59) acid (E-10) G_CC-604-Chloro-2,5-dimethyl-N-[1-[3-oxo- E-10 3-[7-[[(4-Chloro-2,5- F-054-(2-Pyrrolidin-1-yl- 3-[4-(2-pyrrolidin-1-yl-ethyl)- dimethyl- ethyl)piperidine piperidin-1-yl]-propyl]-1H-indol-7- phenyl)sulfonyl]amino]-(F-05) yl]-benzenesulfonic acid amide 1H-indol-1-yl] propionic (G_CC-60)acid (E-10) G_CC-61 4-Chloro-2,5-dimethyl-N-[1-[3-[4-(4- E-103-[7-[[(4-Chloro-2,5- F-21 1-Methyl-4-piperidin-methyl-piperazin-1-yl)-piperidin-1- dimethyl- 4-yl piperazineyl]-3-oxo-propyl]-1H-indol-7-yl]- phenyl)sulfonyl]amino]- (F-21)benzenesulfonic acid amide 1H-indol-1-yl] propionic (G_CC-61) acid(E-10) G_CC-62 4-Chloro-2,5-dimethyl-N-[1-[3-[4- E-103-[7-[[(4-Chloro-2,5- F-22 1-[(1-Methyl-[(1-methyl-piperidin-4-yl)-methyl]- dimethyl- piperidin-4-yl)piperazin-1-yl]-3-oxo-propyl]-1H- phenyl)sulfonyl]amino]- methyl]piperazine indol-7-yl]-benzenesulfonic acid 1H-indol-1-yl] propionic(F-22) amide (G_CC-62) acid (E-10) G_CC-637-Chloro-2-[1-[3-oxo-3-(4-pyridin-4- E-15 3-[6-(4-Chloro-3-oxo-1,2- F-181-Pyridin-4-yl yl-piperazin-1-yl)-propyl]-1H-indol-dihydro-isoindol-2-yl)-1H- piperazine (F-18)6-yl]-2,3-dihydro-isoindol-1-one indol-1-yl] propionic acid (G_CC-63)(E-15) G_CC-64 7-Chloro-2-[1-[3-[4-[(1-methyl- E-153-[6-(4-Chloro-3-oxo-1,2- F-22 1-[(1-Methyl-piperidin-4-yl)-methyl]-piperazin-1- dihydro-isoindol-2-yl)-1H-piperidin-4-yl) yl]-3-oxo-propyl]-1H-indol-6-yl]-2,3- indol-1-yl]propionic acid methyl] piperazine dihydro-isoindol-1-one (G_CC-64)(E-15) (F-22) G_CC-65 4-Chloro-2,5-dimethyl-N-[1-[3-oxo- E-123-[6-[[(4-Chloro-2,5- F-14 3-Pyridin-4-yl-3,9- 3-(3-pyridin-4-yl-3,9-dimethyl- diazaspiro[5.5]undecane diazaspiro[5.5]undecan-9-yl)-phenyl)sulfonyl]amino]- dihydrochloride propyl]-1H-indol-6-yl]-1H-indol-1-yl] propionic (F-14) benzenesulfonic acid amide acid (E-12)(G_CC-65) G_CC-66 8-[3-[6-(4-Chloro-3-oxo-1,2- E-153-[6-(4-Chloro-3-oxo-1,2- F-26 3-[(4-Fluorophenyl)-dihydro-isoindol-2-yl)-1H-indol-1- dihydro-isoindol-2-yl)-1H-methyl]-3,8- yl]-propanoyl]-3-[(4-fluorophenyl)- indol-1-yl] propionicacid diazaspiro[4.5]decan- methyl]-3,8-diazaspiro[4.5]decan-4- (E-15)4-one hydrochloride one (G_CC-66) (F-26) G_CC-677-Chloro-2-[1-[3-oxo-3-(3-pyridin-4- E-15 3-[6-(4-Chloro-3-oxo-1,2- F-143-Pyridin-4-yl-3,9- yl-3,9-diazaspiro[5.5]undecan-9-yl)-dihydro-isoindol-2-yl)-1H- diazaspiro[5.5]undecanepropyl]-1H-indol-6-yl]-2,3-dihydro- indol-1-yl] propionic aciddihydrochloride isoindol-1-one (G_CC-67) (E-15) (F-14) G_CC-687-Chloro-2-[1-[3-oxo-3-(4-pyridin-4- E-15 3-[6-(4-Chloro-3-oxo-1,2- F-244-Piperidin-4- yloxy-piperidin-1-yl)-propyl]-1H-dihydro-isoindol-2-yl)-1H- yloxypyridineindol-6-yl]-2,3-dihydro-isoindol-1- indol-1-yl] propionic acidhydrochloride (F-24) one (G_CC-68) (E-15) G_CC-697-Chloro-2-[1-[3-(4-hydroxy-4- E-15 3-[6-(4-Chloro-3-oxo-1,2- F-194-Pyridin-3-yl pyridin-3-yl-piperidin-1-yl)-3-oxo-dihydro-isoindol-2-yl)-1H- piperidin-4-ol (F-19)propyl]-1H-indol-6-yl]-2,3-dihydro- indol-1-yl] propionic acidisoindol-1-one (G_CC-69) (E-15) G_CC-70 3-[7-[[(4-Chloro-2,5-dimethyl-E-10 3-[7-[[(4-Chloro-2,5- F-13 2-(1-Pyridin-4-yl-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- piperidin-4-yl]-N-[2-(1-pyridin-4-yl-piperidin-4- phenyl)sulfonyl]amino]-yl)ethylamine yl)-ethyl]-propionamide (G_CC-70) 1H-indol-1-yl] propionicdihydrochloride acid (E-10) (F-13) G_CC-713-[6-[[(4-Chloro-2,5-dimethyl- E-12 3-[6-[[(4-Chloro-2,5- F-132-(1-Pyridin-4-yl- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-piperidin-4- yl]-N-[2-(1-pyridin-4-yl-piperidin-4-phenyl)sulfonyl]amino]- yl)ethylamine yl)-ethyl]-propionamide (G_CC-71)1H-indol-1-yl] propionic dihydrochloride acid (E-12) (F-13) G_CC-723-[6-(4-Chloro-3-oxo-1,2-dihydro- E-15 3-[6-(4-Chloro-3-oxo-1,2- F-132-(1-Pyridin-4-yl- isoindol-2-yl)-1H-indol-1-yl]-N-[2-(1-dihydro-isoindol-2-yl)-1H- piperidin-4-pyridin-4-yl-piperidin-4-yl)-ethyl]- indol-1-yl] propionic acidyl)ethylamine propionamide (G_CC-72) (E-15) dihydrochloride (F-13)G_CC-73 3-[7-[[(4-Chloro-2,5-dimethyl- E-10 3-[7-[[(4-Chloro-2,5- F-08[1-(2-Aminoethyl)-4- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-thiophen-2-yl- yl]-N-[2-(4-dimethylamino-4- phenyl)sulfonyl]amino]-piperidin-4-yl]- thiophen-2-yl-piperidin-1-yl)-ethyl]- 1H-indol-1-yl]propionic dimethylamine propionamide (G_CC-73) acid (E-10)trihydrochloride (F-08) G_CC-74 3-[6-[[(4-Chloro-2,5-dimethyl- E-123-[6-[[(4-Chloro-2,5- F-08 [1-(2-Aminoethyl)-4-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- thiophen-2-yl-yl]-N-[2-(4-dimethylamino-4- phenyl)sulfonyl]amino]- piperidin-4-yl]-thiophen-2-yl-piperidin-1-yl)-ethyl]- 1H-indol-1-yl] propionicdimethylamine propionamide (G_CC-74) acid (E-12) trihydrochloride (F-08)G_CC-76 2-[6-[[(4-Methoxy-2,6-dimethyl- E-03 2-[6-[[(4-Methoxy-2,6- F-48Methyl-[3-(4-pyridin- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-4-yl-piperazin-1-yl)- yl]-N-methyl-N-[3-(4-pyridin-4-yl-phenyl)sulfonyl]amino]- propyl]-amine piperazin-1-yl)-propyl]-acetamide1H-indol-1-yl]-acetic acid trihydrochloride (G_CC-76) (E-03) (F-48)G_CC-77 N-[2-(4-Dimethylamino-4-phenyl- E-02 2-[7-[[(4-Methoxy-2,6- F-45Dimethyl-[4-(2- cyclohexyl)-ethyl]-2-[7-[[(4- dimethyl-methylamino-ethyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1-phenyl- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]-acetic acidcyclohexyl]-amine yl]-N-methyl-acetamide (G_CC-77) (E-02)dihydrochloride (F-45) G_CC-81 N-[2-[4-(3-Fluorophenyl)-4-(4- E-053-[6-[[(4-Methoxy-2,6- F-47 2-[4-(3- methyl-piperazin-1-yl)-piperidin-1-dimethyl- Fluorophenyl)-4-(4- yl]-ethyl]-3-[6-[[(4-methoxy-2,6-phenyl)sulfonyl]amino]- methyl-piperazin-1-dimethyl-phenyl)sulfonyl]amino]- 1H-indol-1-yl]-propionicyl)-piperidin-1-yl]- 1H-indol-1-yl]-N-methyl- acid (E-05)ethyl-methyl-amine propionamide (G_CC-81) tetrahydrochloride (F-47)G_CC-84 N-[1-[2-[4-(3-Fluorophenyl)-4-(4- E-02 2-[7-[[(4-Methoxy-2,6-F-46 1-[4-(3- methyl-piperazin-1-yl)-piperidin-1- dimethyl-Fluorophenyl)- yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-phenyl)sulfonyl]amino]- piperidin-4-yl]-4- methoxy-2,6-dimethyl-1H-indol-1-yl]-acetic acid methyl-piperazine benzenesulfonic acid amide(E-02) dihydrochloride (G_CC-84) (F-46) G_CC-882-[7-[[(4-Methoxy-2,6-dimethyl- E-02 2-[7-[[(4-Methoxy-2,6- F-48Methyl-[3-(4-pyridin- phenyl)sulfonyl]amino]-1H-indol-1- dimethyl-4-yl-piperazin-1-yl)- yl]-N-methyl-N-[3-(4-pyridin-4-yl-phenyl)sulfonyl]amino]- propyl]-amine piperazin-1-yl)-propyl]-acetamide1H-indol-1-yl]-acetic acid trihydrochloride (G_CC-88) (E-02) (F-48)G_CC-91 4-Methoxy-2,6-dimethyl-N-[1-[2- E-02 2-[7-[[(4-Methoxy-2,6- F-143-Pyridin-4-yl-3,9- oxo-2-(3-pyridin-4-yl-3,9- dimethyl-diazaspiro[5.5]- diazaspiro[5.5]undecan-9-yl)-ethyl]-phenyl)sulfonyl]amino]- undecane 1H-indol-7-yl]-benzenesulfonic acid1H-indol-1-yl]-acetic acid dihydrochloride amide (G_CC-91) (E-02) (F-14)G_CC-92 4-Methoxy-2,6-dimethyl-N-[1-[2- E-02 2-[7-[[(4-Methoxy-2,6- F-244-Piperidin-4-yloxy- oxo-2-(4-pyridin-4-yloxy-piperidin-1- dimethyl-pyridine yl)-ethyl]-1H-indol-7-yl]- phenyl)sulfonyl]amino]-hydrochloride (F-24) benzenesulfonic acid amide 1H-indol-1-yl]-aceticacid (G_CC-92) (E-02) G_CC-95 N-[2-(4-Dimethylamino-4-phenyl- E-032-[6-[[(4-Methoxy-2,6- F-45 Dimethyl-[4-(2-cyclohexyl)-ethyl]-2-[6-[[(4- dimethyl- methylamino-ethyl)-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]- 1-phenyl-phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]-acetic acidcyclohexyl]-amine yl]-N-methyl-acetamide (G_CC-95) (E-03)dihydrochloride (F-45) G_CC-99 N-[2-[4-(3-Fluorophenyl)-4-(4- E-032-[6-[[(4-Methoxy-2,6- F-47 2-[4-(3- methyl-piperazin-1-yl)-piperidin-1-dimethyl- Fluorophenyl)-4-(4- yl]-ethyl]-2-[6-[[(4-methoxy-2,6-phenyl)sulfonyl]amino]- methyl-piperazin-1-dimethyl-phenyl)sulfonyl]amino]- 1H-indol-1-yl]-acetic acidyl)-piperidin-1-yl]- 1H-indol-1-yl]-N-methyl-acetamide (E-03)ethyl-methyl-amine (G_CC-99) tetrahydrochloride (F-47) G_CC-102N-[2-[4-(3-Fluorophenyl)-4-(4- E-02 2-[7-[[(4-Methoxy-2,6- F-47 2-[4-(3-methyl-piperazin-1-yl)-piperidin-1- dimethyl- Fluorophenyl)-4-(4-yl]-ethyl]-2-[7-[[(4-methoxy-2,6- phenyl)sulfonyl]amino]-methyl-piperazin-1- dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetic acid yl)-piperidin-1-yl]-1H-indol-1-yl]-N-methyl-acetamide (E-02) ethyl-methyl-amine (G_CC-102)tetrahydrochloride (F-47) G_CC-103 2-[6-(4-Chloro-3-oxo-1,2-dihydro-E-16 2-[6-(4-Chloro-3-oxo-1,2- F-13 2-(1-Pyridin-4-yl-isoindol-2-yl)-1H-indol-1-yl]-N-[2-(1- dihydro-isoindol-2-yl)-1H-piperidin-4-yl)-ethyl- pyridin-4-yl-piperidin-4-yl)-ethyl]-indol-1-yl]-acetic acid amine acetamide (G_CC-103) (E-16)dihydrochloride (F-13) G_CC-106 7-Chloro-2-[1-[3-oxo-3-(3-pyridin-4-E-17 3-[7-(4-Chloro-3-oxo-1,2- F-14 3-Pyridin-4-yl-3,9-yl-3,9-diazaspiro[5.5]undecan-9-yl)- dihydro-isoindol-2-yl)-1H-diazaspiro[5.5]- propyl]-1H-indol-7-yl]-2,3-dihydro-indol-1-yl]-propionic acid undecane isoindol-1-one (G_CC-106) (E-17)dihydrochloride (F-14) G_CC-108 N-[[1-[2-[6-[[(4-Methoxy-2,6- E-032-[6-[[(4-Methoxy-2,6- F-34 N-[[4-(4-Methyl-dimethyl-phenyl)sulfonyl]amino]- dimethyl- piperazin-1-yl)-1H-indol-1-yl]-acetyl]-4-(4-methyl- phenyl)sulfonyl]amino]-piperidin-4-yl]- piperazin-1-yl)-piperidin-4-yl]- 1H-indol-1-yl]-aceticacid methyl]-pyridine-4- methyl]-pyridine-4-carboxylic acid (E-03)carboxylic acid amide (G_CC-108) amide dihydrochloride (F-34) G_CC-1112-[6-(4-Chloro-3-oxo-1,2-dihydro- E-16 2-[6-(4-Chloro-3-oxo-1,2- F-15(1-Pyridin-4-yl- isoindol-2-yl)-1H-indol-1-yl]-N-[(1-dihydro-isoindol-2-yl)-1H- piperidin-4-yl)-pyridin-4-yl-piperidin-4-yl)-methyl]- indol-1-yl]-acetic acidmethyl-amine acetamide (G_CC-111) (E-16) dihydrochloride (F-15) G_CC-1132-[6-(4-Chloro-3-oxo-1,2-dihydro- E-16 2-[6-(4-Chloro-3-oxo-1,2- F-472-[4-(3- isoindol-2-yl)-1H-indol-1-yl]-N-[2-[4-dihydro-isoindol-2-yl)-1H- Fluorophenyl)-4-(4-(3-fluorophenyl)-4-(4-methyl- indol-1-yl]-acetic acidmethyl-piperazin-1- piperazin-1-yl)-piperidin-1-yl]-ethyl]- (E-16)yl)-piperidin-1-yl]- N-methyl-acetamide (G_CC-113) ethyl-methyl-aminetetrahydrochloride (F-47) G_CC-116 3-[6-[[(4-Methoxy-2,6-dimethyl- E-053-[6-[[(4-Methoxy-2,6- F-48 Methyl-[3-(4-pyridin-phenyl)sulfonyl]amino]-1H-indol-1- dimethyl- 4-yl-piperazin-1-yl)-yl]-N-methyl-N-[3-(4-pyridin-4-yl- phenyl)sulfonyl]amino]- propyl]-aminepiperazin-1-yl)-propyl]- 1H-indol-1-yl]-propionic trihydrochloridepropionamide (G_CC-116) acid (E-05) (F-48) G_CC-117N-[2-(4-Dimethylamino-4-phenyl- E-05 3-[6-[[(4-Methoxy-2,6- F-45Dimethyl-[4-(2- cyclohexyl)-ethyl]-3-[6-[[(4- dimethyl-methylamino-ethyl)- methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-1-phenyl- phenyl)sulfonyl]amino]-1H-indol-1- 1H-indol-1-yl]-propioniccyclohexyl]-amine yl]-N-methyl-propionamide acid (E-05) dihydrochloride(G_CC-117) (F-45) G_CC-119 3-[6-(4-Chloro-3-oxo-1,2-dihydro- E-153-[6-(4-Chloro-3-oxo-1,2- F-48 Methyl-[3-(4-pyridin-isoindol-2-yl)-1H-indol-1-yl]-N- dihydro-isoindol-2-yl)-1H-4-yl-piperazin-1-yl)- methyl-N-[3-(4-pyridin-4-yl- indol-1-yl]-propionicacid propyl]-amine piperazin-1-yl)-propyl]- (E-15) trihydrochloridepropionamide (G_CC-119) (F-48) G_CC-120 4-Methoxy-2,6-dimethyl-N-[1-[2-E-03 2-[6-[[(4-Methoxy-2,6- F-05 4-(2-Pyrrolidin-1-yl-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)- dimethyl- ethyl)-piperidinepiperidin-1-yl]-ethyl]-1H-indol-6-yl]- phenyl)sulfonyl]amino]- (F-05)benzenesulfonic acid amide 1H-indol-1-yl]-acetic acid (G_CC-120) (E-03)G_CC-123 3-[7-(4-Chloro-3-oxo-1,2-dihydro- E-173-[7-(4-Chloro-3-oxo-1,2- F-15 (1-Pyridin-4-yl-isoindol-2-yl)-1H-indol-1-yl]-N-[(1- dihydro-isoindol-2-yl)-1H-piperidin-4-yl)- pyridin-4-yl-piperidin-4-yl)-methyl]-indol-1-yl]-propionic acid methyl-amine propionamide (G_CC-123) (E-17)dihydrochloride (F-15) G_CC-127 3-[6-(4-Chloro-3-oxo-1,2-dihydro- E-153-[6-(4-Chloro-3-oxo-1,2- F-45 Dimethyl-[4-(2-isoindol-2-yl)-1H-indol-1-yl]-N-[2-(4- dihydro-isoindol-2-yl)-1H-methylamino-ethyl)- dimethylamino-4-phenyl- indol-1-yl]-propionic acid1-phenyl- cyclohexyl)-ethyl]-N-methyl- (E-15) cyclohexyl]-aminepropionamide (G_CC-127) dihydrochloride (F-45) G_CC-1287-Chloro-2-[1-[2-[4-(3-fluoro- E-16 2-[6-(4-Chloro-3-oxo-1,2- F-461-[4-(3-Fluoro- phenyl)-4-(4-methyl-piperazin-1-yl)-dihydro-isoindol-2-yl)-1H- phenyl)-piperidin-4-piperidin-1-yl]-2-oxo-ethyl]-1H- indol-1-yl]-acetic acid yl]-4-methyl-indol-6-yl]-2,3-dihydro-isoindol-1- (E-16) piperazine one (G_CC-128)dihydrochloride (F-46) G_CC-138 2-[6-(4-Chloro-3-oxo-1,2-dihydro- E-162-[6-(4-Chloro-3-oxo-1,2- F-48 Methyl-[3-(4-pyridin-isoindol-2-yl)-1H-indol-1-yl]-N- dihydro-isoindol-2-yl)-1H-4-yl-piperazin-1-yl)- methyl-N-[3-(4-pyridin-4-yl- indol-1-yl]-aceticacid propyl]-amine piperazin-1-yl)-propyl]-acetamide (E-16)trihydrochloride (G_CC-138) (F-48) G_CC-1394-Methoxy-2,6-dimethyl-N-[1-[2- E-02 2-[7-[[(4-Methoxy-2,6- F-37Piperazin-1-yl- oxo-2-[4-(pyridine-3-carbonyl)- dimethyl- pyridin-3-yl-piperazin-1-yl]-ethyl]-1H-indol-7-yl]- phenyl)sulfonyl]amino]- methanone(F-37) benzenesulfonic acid amide 1H-indol-1-yl]-acetic acid (G_CC-139)(E-02)Pharmacological Data

The pharmacological data was determined as described above. Thefollowing data is provided in the table below by way of example:

B1R antagonism, B1R antagonism, rat [10 μM] human [10 μM] Compound %inhibition % inhibition G-01 78 98 G-02 100 95 G-03 90 G-04 62 68 G-0596 100 G-06 70 83 G-07 100 96 G-08 97 98 G-10 76 100 G-11 −21 46 G-12 9298 G-13 96 73 G-14 96 99 G-15 54 81 G-16 96 100 G-17 95 100 G-18 99 99G-19 94 97 G-20 13 43 G-21 43 99 G-22 99 100 G-23 106 100 G-24 103 98G-26 102 98 G-27 99 96 G-31 54 80 G-33 46 93 G_CC-1 62 G_CC-2 70 46G_CC-3 82 G_CC-4 99 G_CC-5 59 G_CC-6 73 G_CC-7 100 G_CC-8 100 26 G_CC-965 G_CC-10 69 G_CC-11 87 G_CC-12 58 G_CC-13 58 G_CC-14 86 G_CC-15 65G_CC-16 67 G_CC-17 52 G_CC-18 87 G_CC-19 68 G_CC-20 86 G_CC-21 97G_CC-22 59 G_CC-23 63 G_CC-24 89 G_CC-25 58 G_CC-26 81 G_CC-27 56G_CC-28 82 G_CC-29 92 G_CC-30 53 G_CC-31 91 G_CC-32 101 73 G_CC-33 71G_CC-34 58 G_CC-35 72 G_CC-36 63 G_CC-37 91 G_CC-38 96 G_CC-39 95G_CC-40 86 G_CC-41 76 G_CC-42 66 G_CC-43 103 100 G_CC-44 73 G_CC-45 59G_CC-46 94 G_CC-47 102 100 G_CC-48 59 G_CC-49 92 G_CC-50 62 G_CC-51 93G_CC-52 100 G_CC-53 101 G_CC-54 96 99 G_CC-56 54 G_CC-57 100 G_CC-59 87G_CC-60 87 G_CC-61 79 G_CC-62 99 94 G_CC-63 100 G_CC-64 89 G_CC-65 53G_CC-66 52 G_CC-67 95 99 G_CC-68 69 G_CC-69 65 G_CC-70 100 G_CC-71 54G_CC-72 71 G_CC-73 55 G_CC-74 51 G_CC-76 104 92 G_CC-77 104 G_CC-81 103G_CC-84 102 G_CC-88 101 100 G_CC-91 100 100 G_CC-92 98 G_CC-95 96G_CC-99 93 G_CC-102 89 G_CC-103 88 G_CC-106 86 G_CC-108 84 G_CC-111 81G_CC-113 78 G_CC-116 74 G_CC-117 74 G_CC-119 72 G_CC-120 72 G_CC-123 67G_CC-127 63 G_CC-128 61 G_CC-138 52 G_CC-139 50

The foregoing description and examples have been set forth merely toillustrate the invention and are not intended to be limiting. Sincemodifications of the described embodiments incorporating the spirit andsubstance of the invention may occur to persons skilled in the art, theinvention should be construed broadly to include all variations withinthe scope of the appended claims and equivalents thereof.

The invention claimed is:
 1. A substituted indole compound correspondingto the formula (I):

wherein T denotes CH; q=1, 2 or 3; s=0 or 1; t=0, 1, 2 or 3; D inposition a or b is bound to the indole skeleton and denotes the groupD2:

wherein y denotes 0 or 1; R³ denotes aryl, heteroaryl or an aryl orheteroaryl bound via a C₁₋₃ alkylene group, wherein aryl and heteroarylcan each be anellated with a 4-, 5-, 6- or 7-membered, saturated ormono- or polyunsaturated but not aromatic cyclic structure whichoptionally may be substituted at one or more of its carbon ring memberswith one or more substituents each independently selected from the groupconsisting of F, Cl, Br, I, —CF₃, —O—CF₃, C₁₋₆ alkyl and O—C₁₋₆ alkyland which optionally may contain one or more heteroatoms or heteroatomgroups independently selected from the group consisting of N, NR^(50a),O, S, S═O and S(═O)₂, wherein R^(50a) denotes H, C₁₋₆ alkyl,—C(═O)—R^(51a), C₃₋₈ cycloalkyl, aryl, heteroaryl or a C₃₋₈ cycloalkyl,aryl or heteroaryl bound via a C₁₋₃ alkylene group and R^(51a) denotesC₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl or a C₃₋₈ cycloalkyl, arylor heteroaryl bound via a C₁₋₃ alkylene group; R⁴ denotes H, C₁₋₆ alkyl,C₃₋₈ cycloalkyl, aryl or heteroaryl or a C₃₋₈ cycloalkyl, aryl orheteroaryl bound via a C₁₋₆ alkylene group; R²⁰⁰ denotes 0 to 2substituents each independently selected from the group consisting of F,Cl, Br, I, CF₃, OCF₃, OH, O—C₁₋₆ alkyl, C₁₋₆ alkyl, aryl and heteroaryland/or two adjacent substituents R²⁰⁰ form an anellated aryl orheteroaryl ring; R²¹⁰ denotes 0 to 3 substituents each independentlyselected from the group consisting of F, Cl, Br, I, CF₃, OCF₃, OH,O—C₁₋₆ alkyl, C₁₋₆ alkyl, aryl and heteroaryl; R⁸ denotes H, C₁₋₆ alkyl,C₃₋₈ cycloalkyl, aryl or heteroaryl or a C₃₋₈ cycloalkyl, aryl orheteroaryl bound via a C₁₋₆ alkylene group; R^(9a) and R^(9b) eachindependently denote H, F, Cl, OH, C₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈cycloalkyl, aryl or heteroaryl or a C₃₋₈ cycloalkyl, aryl or heteroarylbound via a C₁₋₆ alkylene group; A denotes N or CH; with the provisothat if s denotes 1 and t denotes 0, then A denotes CH; and with theproviso that if s and t each denote 0 then A denotes N; R¹⁰ and R¹¹together with A represent a spirocyclic or cyclic group corresponding toformula (II) or formula (III):

wherein c, d, e, f, u and v each independently denote 0, 1 or 2; R¹²,R¹³ and R²⁷ each independently denote 0 to 4 substituents eachindependently selected from the group consisting of F, Cl, OH, ═O, C₁₋₆alkyl, O—C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl, and C₃₋₈cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group, and/ortwo of the 0 to 4 substituents R²⁷ together represent a C₁₋₃ alkylenebridge such that the cyclic structure of formula (III) assumes abicyclically bridged form, and/or two adjacent substituents out of the 0to 4 substituents R¹³ form an anellated aryl or heteroaryl ring, and/ortwo adjacent substituents out of the 0 to 4 substituents R²⁷ form ananellated aryl or heteroaryl ring; X denotes CR^(14a)R^(14b), NR¹⁵ or O;Y denotes CR^(16a)R^(16b), NR¹⁷ or O; with the proviso that if Y denotesNR¹⁷, then X does not denote NR¹⁵; and with the proviso that X and Y donot simultaneously denote O; wherein R^(14a), R^(14b), R^(16a) andR^(16b) each independently denote H, F, Cl, OH, C₁₋₆ alkyl, O—C₁₋₆alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or denote a C₃₋₈ cycloalkyl,aryl or heteroaryl bound via a C₁₋₆ alkylene group, and/or R^(14a) andR^(14b) can together denote ═O, and/or R^(16a) and R^(16b) can togetherdenote ═O; R¹⁵ and R¹⁷ each independently denote H, C₁₋₆ alkyl, C₃₋₈cycloalkyl, aryl or heteroaryl or denote a C₃₋₈ cycloalkyl, aryl orheteroaryl bound via a C₁₋₆ alkylene group; Z in formula (II) denotesCR^(18a)R^(18b), NR¹⁹ or O; or if X denotes O and f denotes 0, then Z informula (II) denotes —(C(R¹²⁴)—C(R¹²⁵))—, wherein R¹²⁴ and R¹²⁵ togetherwith the carbon atoms linking them form a fused aryl or heteroaryl ring;or if X denotes O and f denotes 0, then Z in formula (II) denotes═(N(CR¹²⁶))—, wherein the N atom is singly bound to the O atom, and R¹²⁶denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or denotes aC₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group; Zin formula (III) denotes CR^(18a)R^(18b), NR¹⁹, O, S, S(═O) or S(═O)₂;wherein R^(18a) denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl orheteroaryl or denotes a C₃₋₈ cycloalkyl, aryl or heteroaryl bound via aC₁₋₆ alkylene group, or R^(18a) denotes a group corresponding to formula(IV):

wherein i and j each independently denote 0 or 1; E denotes N or CH,with the proviso that if i denotes 1 and j denotes 0, then E denotes CH;R³⁴ and R³⁵ each independently denote H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl,aryl or heteroaryl or an aryl, heteroaryl or C₃₋₈ cycloalkyl bound via aC₁₋₃ alkylene group; or R³⁴ and R³⁵ together with E form a 5- or6-membered aryl or heteroaryl ring; or R³⁴ and R³⁵ together with E forma saturated heterocyclic structure corresponding to formula (V):

 wherein h and g each independently denote 0, 1 or 2; G denotesCR^(37a)R^(37b), NR³⁸, O, S, S═O or S(═O)₂, with the proviso that if Edenotes CH, then G does not denote CR^(37a)R^(37b); R³⁶ denotes 0 to 4substituents which are each independently selected from the groupconsisting of F, Cl, Br, I, OH, SH, ═O, O—C₁₋₆ alkyl, C₁₋₆ alkyl, C₃₋₈cycloalkyl, aryl, heteroaryl and C₃₋₈ cycloalkyl, aryl or heteroarylbound via a C₁₋₆ alkylene group, and/or two adjacent substituents R³⁶together represent an anellated aryl or heteroaryl ring; R^(37a) andR^(37b) each independently denote H, F, Cl, Br, I, OH, SH, ═O, O—C₁₋₆alkyl, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or denote a C₃₋₈cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group; R³⁸denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or denotes anaryl, heteroaryl or C₃₋₈ cycloalkyl bound via a C₁₋₃ alkylene group;R^(18b) denotes H, OH, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, O—C₁₋₆ alkyl,O—(C₃₋₈ cycloalkyl), (C₁₋₆ alkylene)-O—C₁₋₆ alkyl, (C₁₋₆alkylene)-O—(C₃₋₈ cycloalkyl), aryl, heteroaryl, O-aryl or O-heteroarylor denotes an aryl, O-aryl, heteroaryl or O-heteroaryl bound via a C₁₋₆alkylene group; or R^(18b) denotes a group corresponding to formula(VI):

wherein k denotes 0 or 1; R³⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl,aryl or heteroaryl or denotes a C₃₋₈ cycloalkyl, aryl or heteroarylbound via a C₁₋₃ alkylene group; R⁴⁰ denotes C₁₋₆ alkyl, C₃₋₈cycloalkyl, aryl or heteroaryl or denotes a C₃₋₈ cycloalkyl, aryl orheteroaryl bound via a C₁₋₆ alkylene group; or R³⁹ and R⁴⁰ together withthe N—C(═O) group linking them form a ring corresponding to formula(VII):

wherein I denotes 0, 1 or 2; and R⁴¹ and R⁴² together with the carbonatoms linking them form an anellated aryl or heteroaryl ring; R¹⁹denotes H; or (P)_(z)—R²², wherein z denotes 0 or 1; P denotes (C═O),S(═O)₂ or C(═O)—N(R²⁴), wherein the N atom in the C(═O)—N(R²⁴) group islinked to R²², wherein R²⁴ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or anaryl, heteroaryl or C₃₋₈ cycloalkyl bound via a C₁₋₃ alkylene group; R²²denotes C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl or heteroaryl or an aryl orheteroaryl bound via a C₁₋₆ alkylene group; or R²² denotes a groupcorresponding to formula (VIII):

wherein n denotes 0, 1 or 2; m denotes 0, 1 or 2; w denotes 0 or 1, Mdenotes CH or N; with the proviso that if P denotes C(═O)—NR²⁴ and wdenotes 0, then M denotes CH; and with the proviso that if z and wsimultaneously each denote 0, then M denotes CH; R⁴³ denotes 0 to 4substituents each independently selected from the group consisting of F,Cl, OH, ═O, O₁₋₆ alkyl, O—C₁₋₆ alkyl, C₃₋₈ cycloalkyl, aryl, heteroaryl,and C₃₋₈ cycloalkyl, aryl or heteroaryl bound via a C₁₋₆ alkylene group,and/or two adjacent substituents out of the 0 to 4 substituents R⁴³together represent an anellated aryl or heteroaryl ring; and L denotesCR^(44a)R^(44b), NR⁴⁵,O, S, S═O or S(═O)₂; wherein  R^(44a) and R^(44b)each independently denote H, F, Cl, Br, I, OH, C₁₋₆ alkyl, O—C₁₋₆ alkyl,C₃₋₈ cycloalkyl, aryl or heteroaryl, or a C₃₋₈ cycloalkyl, aryl orheteroaryl bound via a C₁₋₆ alkylene group; or  R^(44a) and R^(44b)together denote ═O; and  R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl,aryl or heteroaryl or denotes an aryl, heteroaryl or C₃₋₈ cycloalkylbound via a C₁₋₃ alkylene group; wherein the aforementioned C₁₋₆ alkyl,C₁₋₃ alkylene and C₁₋₆ alkylene groups may each be branched orunbranched, and the aforementioned C₁₋₆ alkyl, C₁₋₃ alkylene, C₁₋₆alkylene, C₃₋₈ cycloalkyl, aryl and heteroaryl groups may each beunsubstituted or mono- or polysubstituted with identical or differentsubstituents; or a physiologically compatible salt thereof.
 2. Acompound according to claim 1, wherein said compound is in the form of amixture of stereoisomers in any mixing ratio.
 3. A compound according toclaim 2, wherein said mixture is a racemic mixture.
 4. A compoundaccording to claim 1, wherein said compound is in the form of anisolated stereoisomer.
 5. A compound according to claim 1, wherein R³denotes an unsubstituted or mono- or identically or differentlypolysubstituted aryl or heteroaryl group selected from the groupconsisting of phenyl, naphthyl, chromanyl, indolyl, benzofuranyl,benzothiophenyl; benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl,thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl,imidazothiazolyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl, or aphenyl or naphthyl bound via an unsubstituted or mono- or identically ordifferently polysubstituted C₁₋₃ alkylene group; wherein substituents ofsaid aryl or heteroaryl groups are each independently selected from thegroup consisting of —O—C₁₋₃ alkyl, C₁₋₆ alkyl, F, Cl, Br, I, CF₃, OCF₃,OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl, andsubstituents of said alkylene groups are each independently selectedfrom the group consisting of —O—C₁₋₃ alkyl, F, Cl, Br, I, CF₃, OCF₃, OH,SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl, and R⁴ isselected from the group consisting of H, methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and cyclopropyl. 6.A compound according to claim 5, wherein R³ is an unsubstituted or mono-or polysubstituted phenyl, naphthyl, chromanyl, benzothiophenyl,benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranylgroup or an unsubstituted or mono- or polysubstituted phenyl group boundvia a C₁₋₃ alkylene group.
 7. A compound according to claim 1, whereinR⁸ denotes H, branched or unbranched C₁₋₆ alkyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, —CH₂CF₃, phenyl, benzyl,phenylethyl, phenylpropyl; or cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl bound via a C₁₋₃ alkylene group, each unsubstituted or mono-or polysubstituted with identical or different substituents.
 8. Acompound according to claim 1, wherein R^(9a) and R^(9b) each eachindependently denote H, F, methyl, ethyl, isopropyl, CF₃, methoxy,cyclopropyl, phenyl, benzyl, phenylethyl, C₁₋₃ alkylene-cyclopropyl,C₁₋₃ alkylene-cyclobutyl, C₁₋₃ alkylene-cyclopentyl, C₁₋₃alkylene-cyclohexyl or C₁₋₃ alkylene-CF₃, each unsubstituted or mono- orpolysubstituted with identical or different substituents.
 9. A compoundaccording to claim 8, wherein R^(9a) and R^(9b) both denote H.
 10. Acompound according to claim 1, wherein (a1) the formula (II) assumes thefollowing substructure (IIa):

or (a2) the formula (III) assumes one of the following substructures(IIIa) or (III b):


11. A compound according to claim 10, wherein (a1) the substructurehaving formula (IIa) assumes the following substructure (IIb):

or (a2) the substructures having formulas (IIIa) and (IIIb) assume oneof the following substructures (IIIc), (IIId), (IIIe) or (IIIf):


12. A compound according to claim 11, wherein (a1) the substructurehaving formula (IIa) assumes the substructure (IIb), and s and t eachdenote 0; or (a2) the substructures having formulas (IIIa) and (IIIb)assume one of the substructures (IIIc) or (IIId), and s and t eachdenote 0; or (a3) the substructures having formulas (IIIa) and (IIIb)assume one of the substructures (IIIc) or (IIId), and two of thesubstituents R²⁷ together form a C₁₋₃ alkylene bridge such that thecyclic compound represented in substructure (IIIc) or (IIId) assumes abicyclically bridged form, and s and t each denote 0; or (a4) thesubstructures having formulas (IIIa) and (IIIb) assume one of thesubstructures (IIIc), (IIId), (IIIe) or (IIIf); s denotes 1; t denotes0, 1, 2 or 3; R⁸ denotes H, C₁₋₆ alkyl or C₃₋₆ cycloalkyl, in each caseunsubstituted or mono- or polysubstituted with identical or differentsubstituents, and R^(9a) and R^(9b) each independently denote H, C₁₋₆alkyl or C₃₋₆ cycloalkyl.
 13. A compound according to claim 1, wherein(a1) s and t each denote 0, and formula (II) assumes the followingsubstructure (IIc)

wherein c, d, e and f each each independently denote 0, 1 or 2; Xdenotes CR^(14a)R^(14b), NR¹⁵ or O, Z denotes CR^(18a)R^(18b) or NR¹⁹,or if X denotes O and f denotes 0, then Z may denote ═(N(CR¹²⁶))—,wherein the N atom is singly bound to the O atom; wherein R¹²⁶ denotesH, C₁₋₄ alkyl or an unsubstituted or mono- or polysubstituted phenyl,pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyloptionally bound via a C₁₋₃ alkylene group, wherein the substituents areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl, R^(14a), R^(14b), R^(16a) and R^(16b)each independently denote H or an unsubstituted or mono- orpolysubstituted phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl optionally bound via a C₁₋₃ alkylene group, whereinthe substituents are each independently selected from the groupconsisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, and/orR^(16a) and R^(16b) together denote ═O; R¹⁵ denotes H, C₁₋₄ alkyl or anunsubstituted or mono- or polysubstituted phenyl, pyridyl, imidazolyl,triazolyl, pyrimidyl, thiazolyl or thienyl optionally bound via a C₁₋₃alkylene group, wherein the substituents are selected from the groupconsisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, R^(18a)denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl), —N(C₁₋₆alkyl)₂, unsubstituted or mono- or polysubstituted phenyl, pyridyl,imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, or unsubstitutedor mono- or polysubstituted phenyl, pyridyl, imidazolyl, triazolyl,pyrimidyl, thiazolyl or thienyl bound by an —(O)₀₋₁—C₁₋₆ alkylene group;wherein the substituents are each each independently selected from thegroup consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl;or R^(18a) denotes a structure corresponding to formula (IVa)

wherein denotes 0 or 1; j denotes 0 or 1; h and g each independentlydenote 0 or 1, E denotes N or CH; with the proviso that if i denotes 1and j denotes 0, then E denotes CH; G denotes CR^(37a) R^(37b) or NR³⁸;wherein R^(37a) and R^(37b) each independently denote H; F or C₁₋₄alkyl, each unsubstituted or mono- or polysubstituted with identical ordifferent substituents; and R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkylor pyridyl; R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl,imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents; phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl bound via a C₁₋₆ alkylene group, each unsubstitutedor mono- or polysubstituted with identical or different substituents;O-phenyl or O-pyridyl, each unsubstituted or mono- or polysubstitutedwith identical or different substituents, phenyl, pyridyl or thienylbridged by C₁₋₆ alkylene-NH(C═O), each unsubstituted or mono- orpolysubstituted with identical or different substituents, wherein thesubstituents are each independently selected from the group consistingof F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹⁹ denotes H,C₁₋₆ alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆ alkylene-NH(C₁₋₆alkyl), C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl, pyridyl, thienyl,thiazolyl, triazolyl, pyrimidinyl or imidazolyl; each unsubstituted ormono- or polysubstituted with identical or different substituents; orphenyl, pyridyl, thienyl, thiazolyl, pyrimidinyl, triazolyl orimidazolyl bound via a C₁₋₆ alkylene group; each unsubstituted or mono-or polysubstituted with identical or different substituents, wherein thesubstituents are independently selected from the group consisting of F,Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl, or a structurecorresponding to formula (VIIIa):

wherein w denotes 0 or 1; n denotes 0 or 1; m denotes 0 or 1; M denotesCH or N, with the proviso that if w denotes 0 then M denotes CH; Ldenotes CR^(44a)R^(44b) or NR⁴⁵; wherein R^(44a) and R^(44b) eachindependently denote H; F or C₁₋₆ alkyl, each unsubstituted or mono- orpolysubstituted with identical or different substituents; and R⁴⁵denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl; or (a2) s and t eachdenote 0 and the formula (III) assumes one of the substructures (IIIc′)or (IIId′)

wherein u and v each independently denote 0, 1 or 2, R^(18a) denotes H,C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl), —N(C₁₋₆ alkyl)₂,unsubstituted or mono- or polysubstituted phenyl, pyridyl, imidazolyl,triazolyl, pyrimidyl, thiazolyl or thienyl, or unsubstituted or mono- orpolysubstituted phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl bound by an —(O)₀₋₁—C₁₋₆ alkylene group; whereinthe substituents are independently selected from the group consisting ofF, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; or R^(18a) denotes astructure corresponding to formula (IVa):

wherein denotes 0 or 1; j denotes 0 or 1; h and g, each independently,denote 0 or 1, E denotes N or CH; with the proviso that if i denotes 1and j denotes 0, then E denotes CH, G denotes CR^(37a) R^(37b) or NR³⁸;wherein R^(37a) and R^(37b) each independently denote H, F, orunsubstituted, monosubstituted or identically or differentlypolysubstituted C₁₋₄ alkyl; and R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆cycloalkyl or pyridyl; or R^(18a) denotes the following structure:

R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl, imidazolyl,triazolyl, pyrimidyl, thiazolyl or thienyl, each unsubstituted or mono-or polysubstituted with identical or different substituents; phenyl,pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl boundvia a C₁₋₆ alkylene group, each unsubstituted or mono- orpolysubstituted with identical or different substituents; O-phenyl orO-pyridyl, each unsubstituted or mono- or polysubstituted with identicalor different substituents, phenyl, pyridyl or thienyl bridged by C₁₋₆alkylene-NH(C═O), each unsubstituted or mono- or polysubstituted withidentical or different substituents, wherein the substituents areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆ alkylene-NH(C₁₋₆ alkyl), C₁₋₆alkylene-N(C₁₋₆ alkyl)₂ or phenyl, pyridyl, thienyl, thiazolyl,triazolyl, pyrimidinyl or imidazolyl; each unsubstituted or mono- orpolysubstituted with identical or different substituents; or phenyl,pyridyl, thienyl, thiazolyl, pyrimidinyl, triazolyl or imidazolyl boundvia a C₁₋₆ alkylene group; each unsubstituted or mono- orpolysubstituted with identical or different substituents, wherein thesubstituents are independently selected from the group consisting of F,Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; or a structurecorresponding to formula (VIIIa):

wherein w denotes 0 or 1; n denotes 0 or 1; m denotes 0 or 1; M denotesCH or N, with the proviso that if w denotes 0 then M denotes CH; Ldenotes CR^(44a)R^(44b) or NR⁴⁵; wherein R^(44a) and R^(44b) eachindependently denote H, F, or unsubstituted, monosubstituted oridentically or differently polysubstituted C₁₋₆ alkyl; and R⁴⁵ denotesH, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl; or (a3) s and t each denote0, and the formula (III) assumes one of the following substructures (A)to (H):

and wherein R^(18a) denotes H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆alkyl), —N(C₁₋₆ alkyl)₂, unsubstituted or mono- or polysubstitutedphenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl,or unsubstituted or mono- or polysubstituted phenyl, pyridyl,imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl bound by an—(O)₀₋₁—C₁₋₆ alkylene group; wherein the substituents are independentlyselected from the group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OHand O—C₁₋₄ alkyl, or R^(18a) denotes a structure corresponding toformula (IVa)

wherein i denotes 0 or 1; j denotes 0 or 1; h and g, each independently,denote 0 or 1, E denotes N or CH; with the proviso that if i denotes 1and j denotes 0, then E denotes CH, G denotes CR^(37a) R^(37b) or NR³⁸;wherein R^(37a) and R^(37b) each independently denote H; F or C₁₋₄alkyl, each unsubstituted or mono- or polysubstituted with identical ordifferent substituents; and R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆ cycloalkylor pyridyl; R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl, pyridyl,imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents; phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl bound via a C₁₋₆ alkylene group, each unsubstitutedor mono- or polysubstituted with identical or different substituents;O-phenyl or O-pyridyl, each unsubstituted or mono- or polysubstitutedwith identical or different substituents, phenyl, pyridyl or thienylbridged by C₁₋₆ alkylene-NH(C═O), each unsubstituted or mono- orpolysubstituted with identical or different substituents, wherein thesubstituents are independently selected from the group consisting of F,Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹⁹ denotes H, C₁₋₆alkyl, C₃₋₈ cycloalkyl, —(C═O)—C₁₋₆ alkyl; C₁₋₆ alkylene-NH(C₁₋₆ alkyl),C₁₋₆ alkylene-N(C₁₋₆ alkyl)₂ or phenyl, pyridyl, thienyl, thiazolyl,triazolyl, pyrimidinyl or imidazolyl; each unsubstituted or mono- orpolysubstituted with identical or different substituents; or phenyl,pyridyl, thienyl, thiazolyl, pyrimidinyl, triazolyl or imidazolyl boundvia a C₁₋₆ alkylene group; each unsubstituted or mono- orpolysubstituted with identical or different substituents, wherein thesubstituents are independently selected from the group consisting of F,Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; or a structurecorresponding to formula (VIIIa)

wherein w denotes 0 or 1; n denotes 0 or 1; m denotes 0 or 1; M denotesCH or N, with the proviso that if w denotes 0, then M denotes CH; Ldenotes CR^(44a)R^(44b) or NR⁴⁵; wherein R^(44a) and R^(44b) eachindependently denote H, F, or unsubstituted, monosubstituted oridentically or differently polysubstituted C₁₋₆ alkyl; and R⁴⁵ denotesH, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl; or (a4) s denotes 1, tdenotes 0, 1, 2 or 3, R⁸ denotes H, C₁₋₄ alkyl or C₃₋₆ cycloalkyl R^(9a)and R^(9b) each independently denote H, C₁₋₄ alkyl or C₃₋₆ cycloalkyl;the formula (III) assumes one of the following substructures (IIIc′),(IIId′), (Ille′) or (IIIf′):

wherein u and v each independently denote 0, 1 or 2, R^(18a) denotes H,C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —NH(C₁₋₆ alkyl), —N(C₁₋₆ alkyl)₂,unsubstituted or mono- or polysubstituted phenyl, pyridyl, imidazolyl,triazolyl, pyrimidyl, thiazolyl or thienyl, or unsubstituted or mono- orpolysubstituted phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl bound by an —(O)₀₋₁—C₁₋₆ alkylene group; whereinthe substituents are independently selected from the group consisting ofF, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; or R^(18a) denotes astructure corresponding to formula (IVa):

wherein i denotes 0 or 1; j denotes 0 or 1; h and g each independentlydenote 0 or 1; E denotes N or CH; with the proviso that if i denotes 1and j denotes 0, then E denotes CH, G denotes CR^(37a) R^(37b) or NR³⁸;wherein R^(37a) and R^(37b) each independently denote H, F, orunsubstituted, monosubstituted or identically or differentlypolysubstituted C₁₋₄ alkyl; and R³⁸ denotes H; C₁₋₆ alkyl, C₃₋₆cycloalkyl or pyridyl; R^(18b) denotes H, OH, C₁₋₆ alkyl, phenyl,pyridyl, imidazolyl, triazolyl, pyrimidyl, thiazolyl or thienyl, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents; phenyl, pyridyl, imidazolyl, triazolyl, pyrimidyl,thiazolyl or thienyl bound via a C₁₋₆ alkylene group, each unsubstitutedor mono- or polysubstituted with identical or different substituents;O-phenyl or O-pyridyl, each unsubstituted or mono- or polysubstitutedwith identical or different substituents, phenyl, pyridyl or thienylbridged by C₁₋₆ alkylene-NH(C═O), each unsubstituted or mono- orpolysubstituted with identical or different substituents independentlyselected from the group consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OHand O—C₁₋₄ alkyl; R¹⁹ denotes H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl,—(C═O)—C₁₋₆ alkyl; C₁₋₆ alkylene-NH(C₁₋₆ alkyl), C₁₋₆ alkylene-N(C₁₋₆alkyl)₂ or phenyl, pyridyl, thienyl, thiazolyl, triazolyl, pyrimidinylor imidazolyl; each unsubstituted or mono- or polysubstituted withidentical or different substituents; or phenyl, pyridyl, thienyl,thiazolyl, pyrimidinyl, triazolyl or imidazolyl bound via a C₁₋₆alkylene group; each unsubstituted or mono- or polysubstituted withidentical or different substituents, wherein the substituents areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl; or a structure corresponding toformula (VIIIa):

wherein w denotes 0 or 1; n denotes 0 or 1; m denotes 0 or 1; M denotesCH or N, with the proviso that if w denotes 0, then M denotes CH; and Ldenotes CR^(44a)R^(44b) or NR⁴⁵; wherein R^(44a) and R^(44b) eachindependently denote H, F, or unsubstituted, monosubstituted oridentically or differently polysubstituted C₁₋₆ alkyl; and R⁴⁵ denotesH, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl.
 14. A compound according toclaim 1, wherein the substructure (II) assumes one of the followingsubstructures:

wherein R¹³ denotes 1 or 2 substituents selected from H andunsubstituted, monosubstituted or identically or differentlypolysubstituted phenyl with substituents independently selected from thegroup consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl;and/or two substituents R¹³ together form ═O; and/or two adjacentsubstituents R¹³ together form an anellated aryl or heteroaryl ringunsubstituted or mono- or polysubstituted with identical or differentsubstituents independently selected from the group consisting of F, Cl,CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹⁵ denotes H; C₁₋₆ alkyl;C₃₋₈ cycloalkyl; unsubstituted, monosubstituted or identically ordifferently polysubstituted phenyl or pyridyl; or unsubstituted,monosubstituted or identically or differently polysubstituted phenyl orpyridyl bound via a C₁₋₆ alkylene group, wherein the substituents areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R^(16a) denotes H; C₁₋₆ alkyl; orunsubstituted, monosubstituted or identically or differentlypolysubstituted phenyl or pyridyl, wherein the substituents areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R^(18a) denotes H; C₁₋₆ alkyl; C₃₋₈cycloalkyl, N(C₁₋₆ alkyl)₂; NH(C₁₋₆ alkyl), azetidinyl; pyrrolidinyl,piperidinyl, 4-(C₁₋₆ alkyl)-piperazinyl; phenyl or pyridyl, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents; or N(C₁₋₆ alkyl)₂; NH(C₁₋₆ alkyl), azetidinyl;pyrrolidinyl, piperidinyl, 4-(C₁₋₆ alkyl)-piperazinyl; phenyl,imidazolyl, triazolyl or pyridyl bound by an —(O)_(0/1)—C₁₋₆ alkylenegroup, each unsubstituted or mono- or polysubstituted with identical ordifferent substituents, wherein the substituents of C₁₋₆ alkyl; C₃₋₈cycloalkyl, azetidinyl; pyrrolidinyl, piperidinyl and 4-(C₁₋₆alkyl)-piperazinyl are independently selected from the group consistingof F, Cl, CF₃, ═O, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; and whereinthe substituents of phenyl, imidazolyl, triazolyl or pyridyl areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R^(18b) denotes H; OH; C₁₋₆ alkyl;phenyl or pyridyl, each unsubstituted or mono- or polysubstituted withidentical or different substituents, or phenyl or pyridyl bound via aC₁₋₆ alkylene group, each unsubstituted or mono- or polysubstituted withidentical or different substituents; wherein the substituents of phenyland pyridyl are independently selected from the group consisting of F,Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹⁹ denotes H; C₁₋₆alkyl; C₃₋₈ cycloalkyl, phenyl, pyridyl, thienyl, imidazolyl, thiazolylor triazolyl, each unsubstituted or mono- or polysubstituted withidentical or different substituents, or phenyl or pyridyl bound via aC₁₋₆ alkylene group or (C═O) group, each unsubstituted or mono- orpolysubstituted with identical or different substituents, wherein thesubstituents of phenyl, pyridyl, thienyl, imidazolyl, thiazolyl andtriazolyl are independently selected from the group consisting of F, Cl,CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl; R¹²⁰ denotes H; F; Cl; OH;OCH₃, O—CF₃, C₁₋₆ alkyl; CF₃; or phenyl which is unsubstituted or mono-or polysubstituted with substituents independently selected from thegroup consisting of F, Cl, CF₃, C₁₋₄ alkyl, OCF₃, OH and O—C₁₋₄ alkyl;and R¹²⁶ denotes H; C₁₋₆ alkyl; C₃₋₆ cycloalkyl; phenyl or pyridyl; orC₃₋₆ cycloalkyl, phenyl or pyridyl bound via a C₁₋₃ alkylene group, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents, wherein the substituents of phenyl and pyridyl areindependently selected from the group consisting of F, Cl, CF₃, C₁₋₄alkyl, OCF₃, OH and O—C₁₋₄ alkyl.
 15. A compound according to claim 1,wherein in formula (I) the following substructure (B)

is selected from the group consisting of:

with the proviso that if s denotes 0, then t likewise denotes 0; M¹, M²and M³ each denote N or CH, wherein one of M¹, M² and M³ denotes N, andthe other two each denote CH; R⁸ denotes H; branched or unbranched C₁₋₆alkyl or C₃₋₆ cycloalkyl, each unsubstituted or mono- or polysubstitutedwith identical or different substituents; R¹⁹ denotes H; C₁₋₆ alkyl orC₃₋₆ cycloalkyl, each unsubstituted or mono- or polysubstituted withidentical or different substituents; R³⁴ and R³⁵ each independentlydenote methyl or ethyl or together with the N-atom linking them form anazetidinyl; pyrrolidinyl, piperidinyl, 4-(C₁₋₆ alkyl)-piperazinyl group,each unsubstituted or mono- or polysubstituted with identical ordifferent substituents; R³⁸ denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl orpyridyl; R³⁹ denotes H; C₁₋₆ alkyl or C₃₋₆ cycloalkyl, eachunsubstituted or mono- or polysubstituted with identical or differentsubstituents; and R⁴⁵ denotes H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl or pyridyl;and R¹⁹⁰ represents 0 to 4 substituents each independently selected fromthe group consisting of F, Cl, O—CF₃, CF₃ and CN.
 16. A compoundaccording to claim 1, selected from the group consisting of: No.Compound G-014-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G-024-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G-034-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyridin-4-yloxy-piperidin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G-044-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(1-oxo-4-phenyl-2,4,8-triazaspiro[4.5]decan-8-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide G-05 4-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide G-064-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amideG-13 4-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(3-(pyridin-4-yl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-14 4-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(8-(pyridin-4-yl)-2,8-diazaspiro[4.5]decan-2-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-164-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(3-(6-(piperidin-1-ylmethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidin-1-yl)ethyl)-1H-indol-7-yl)benzenesulfonicacid amide G-174-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(7-(pyridin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-18N-(1-(2-(9-(azetidin-1-yl)-3-azaspiro[5.5]undecan-3-yl)-2-oxoethyl)-1H-indol-7-yl)-4-methoxy-2,6-dimethylbenzenesulfonic acid amide G-224-Methoxy-2,6-dimethyl-N-(1-(2-oxo-2-(9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)benzenesulfonic acidamide G-24 4-Methoxy-2,6-dimethyl-N-[[1-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-3-yl)-ethyl]-1H-indol-7-yl]-methyl]-benzenesulfonicacid amide G_CC-14-Methoxy-2,6-dimethyl-N-[1-[2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-24-Methoxy-2,6-dimethyl-N-[1-[2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-34-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyrimidin-2-yl-piperazin-1-yl)-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-44-Methoxy-2,6-dimethyl-N-[1-[2-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-5N-[1-[2-[4-(4-fluorophenyl)-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-64-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyrimidin-2-yl-piperazin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-74-Methoxy-2,6-dimethyl-N-[1-[2-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-84-Chloro-2,5-dimethyl-N-[1-[2-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-2-oxo-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-92-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[(1-pyridin-4-yl-piperidin-4-yl)-methyl]-acetamide G_CC-10N-[1-[2-(3-Benzyl-3,7-diazaspiro[4.4]nonan-7-yl)-2-oxo-ethyl]-1H-indol-6-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-11N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-12N-[1-[2-[3-(4-Fluorophenyl)-4-oxo-3,8-diazaspiro[4.5]decan-8-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-13N-[1-[2-(3-Benzyl-3,7-diazaspiro[4.4]nonan-7-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-14N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-152-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[3-(4-dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-N-methyl-acetamideG_CC-16N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-N-methyl-2-[7-[(naphthalen-1-ylsulfonyl)amino]-1H-indol-1-yl]-acetamide G_CC-17N-[4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamide G_CC-18N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-19N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamide G_CC-20N-[1-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-212-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-22N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-233-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-242-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-25N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-N-methyl-2-[7-[(naphthalen-1-ylsulfonyl)amino]-1H-indol-1-yl]-acetamide G_CC-262-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[3-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-N-methyl-acetamideG_CC-272-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-acetamide G_CC-282-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-acetamide G_CC-29N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamideG_CC-30N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetamide G_CC-31N-[1-[2-[1-(4-Fluorophenyl)-3-methyl-4-oxo-3,8-diazaspiro[4.5]decan-8-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acidamide G_CC-32N-[1-[2-(3-Benzyl-4-oxo-3,8-diazaspiro[4.5]decan-8-yl)-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-33N-[1-[2-[2-[(4-Fluorophenyl)-methyl]-2,5-diazabicyclo[2.2.1]heptan-5-yl]-2-oxo-ethyl]-1H-indol-6-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amideG_CC-344-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[2-(pyridin-4-yl-methyl)-2,5-diazabicyclo[2.2.1]heptan-5-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonicacid amide G_CC-354-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-6-yl]-benzenesulfonic acidamide G_CC-364-Chloro-2,5-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-37N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-6-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-38N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-naphthalene-1-sulfonic acid amide G_CC-394-Chloro-2,5-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-404-Methoxy-2,6-dimethyl-N-[1-[3-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-414-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-424-Methoxy-2,6-dimethyl-N-[1-[3-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-434-Methoxy-2,6-dimethyl-N-[1-[3-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-44N-[1-[3-[4-(3-Dimethylamino-propyl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-45N-[1-[3-(4-Hydroxy-4-pyridin-2-yl-piperidin-1-yl)-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-46N-[3-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamideG_CC-473-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-48N-[1-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-3-oxo-propyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide G_CC-49N-[3-(4-Dimethylamino-4-phenyl-piperidin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamideG_CC-50N-[4-(Azetidin-1-yl)-4-phenyl-cyclohexyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-51N-[2-(4-Dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-52N-[1-[3-Oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-7-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-53N-[1-[2-Oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide G_CC-544-Methoxy-2,6-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-7-yl]-benzenesulfonic acidamide G_CC-56N-[3-(4-Ethyl-piperazin-1-yl)-propyl]-3-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-propionamide G_CC-574-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amideG_CC-594-Chloro-2,5-dimethyl-N-[1-[3-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-604-Chloro-2,5-dimethyl-N-[1-[3-oxo-3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-614-Chloro-2,5-dimethyl-N-[1-[3-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-624-Chloro-2,5-dimethyl-N-[1-[3-[4-[(1-methyl-piperidin-4-yl)-methyl]-piperazin-1-yl]-3-oxo-propyl]-1H-indol-7-yl]-benzenesulfonic acid amide G_CC-654-Chloro-2,5-dimethyl-N-[1-[3-oxo-3-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-propyl]-1H-indol-6-yl]-benzenesulfonic acid amide G_CC-703-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-713-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(1-pyridin-4-yl-piperidin-4-yl)-ethyl]-propionamide G_CC-733-[7-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-propionamideG_CC-743-[6-[[(4-Chloro-2,5-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-[2-(4-dimethylamino-4-thiophen-2-yl-piperidin-1-yl)-ethyl]-propionamideG_CC-762-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-acetamide (G_CC-76) G_CC-77N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide(G_CC-77) G_CC-81N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide (G_CC-81) G_CC-84N-[1-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl]-1H-indol-7-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide(G_CC-84) G_CC-882-[7-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-acetamide (G_CC-88) G_CC-914-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecan-9-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acidamide (G_CC-91) G_CC-924-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-(4-pyridin-4-yloxy-piperidin-1-yl)-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide (G_CC-92) G_CC-95N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide(G_CC-95) G_CC-99N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-2-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide (G_CC-99) G_CC-102N-[2-[4-(3-Fluorophenyl)-4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-ethyl]-2-[7-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-acetamide (G_CC-102) G_CC-108N-[[1-[2-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-acetyl]-4-(4-methyl-piperazin-1-yl)-piperidin-4-yl]-methyl]-pyridine-4-carboxylicacid amide (G_CC-108) G_CC-1163-[6-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-N-[3-(4-pyridin-4-yl-piperazin-1-yl)-propyl]-propionamide (G_CC-116)G_CC-117N-[2-(4-Dimethylamino-4-phenyl-cyclohexyl)-ethyl]-3-[6-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-1H-indol-1-yl]-N-methyl-propionamide(G_CC- 117) G_CC-1204-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(2-pyrrolidin-1-yl-ethyl)-piperidin-1-yl]-ethyl]-1H-indol-6-yl]-benzenesulfonic acid amide (G_CC-120) G_CC-1394-Methoxy-2,6-dimethyl-N-[1-[2-oxo-2-[4-(pyridin-3-carbonyl)-piperazin-1-yl]-ethyl]-1H-indol-7-yl]-benzenesulfonic acid amide (G_CC-139)

or a physiologically compatible salt thereof.
 17. A pharmaceuticalcomposition comprising a compound according to claim 1 and at least onepharmaceutically acceptable carrier or auxiliary substance.
 18. A methodof treating or inhibiting a condition selected from the group consistingof pain, inflammation, and obesity, in a subject in need thereof, saidmethod comprising administering to said subject a pharmacologicallyeffective amount of a compound according to claim
 1. 19. A methodaccording to claim 18, wherein said condition is pain selected from thegroup consisting of acute pain, visceral pain, neuropathic pain, chronicpain and inflammatory pain.